Eric I. Knudsen

All Publications

• Neural Circuits That Mediate Selective Attention: A Comparative Perspective. Trends in neurosciences Knudsen, E. I. 2018

  Abstract

  Selective attention is central to cognition. Dramatic advances have been made in understanding the neural circuits that mediate selective attention. Forebrain networks, most elaborated in primates, control all forms of attention based on task demands and the physical salience of stimuli. These networks contain circuits that distribute top-down signals to sensory processing areas and enhance information processing in those areas. A midbrain network, most elaborated in birds, controls spatial attention. It contains circuits that continuously compute the highest priority stimulus location and route sensory information from the selected location to forebrain networks that make cognitive decisions. The identification of these circuits, their functions and mechanisms represent a major advance in our understanding of how the vertebrate brain mediates selective attention.

  View details for DOI 10.1016/j.tins.2018.06.006

  View details for PubMedID 30075867

• Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework. journal of neuroscience Sridharan, D., Steinmetz, N. A., Moore, T., Knudsen, E. I. 2017; 37 (3): 480-511

  Abstract

  Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)-the central structure in the midbrain network-in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or "sensitivity," and those that alter the selective gating of sensory information or "choice bias." Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention.Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice-bias control) are poorly understood. Here, we introduce a model of multialternative decision making that distinguishes bias from sensitivity effects in attention tasks. With our model, we simulate experimental data from four seminal studies that microstimulated or inactivated a key attention-related midbrain structure, the superior colliculus (SC). We demonstrate that the experimental effects of SC manipulation are entirely consistent with the SC controlling attention by changing choice bias, thereby shedding new light on how the brain mediates attention.

  View details for DOI 10.1523/JNEUROSCI.4505-14.2017

  View details for PubMedID 28100734

  View details for PubMedCentralID PMC5242403

• Spatially precise visual gain control mediated by a cholinergic circuit in the midbrain attention network NATURE COMMUNICATIONS Asadollahi, A., Knudsen, E. I. 2016; 7

  Abstract

  A primary function of the midbrain stimulus selection network is to compute the highest-priority location for attention and gaze. Here we report the contribution of a specific cholinergic circuit to this computation. We functionally disconnected the tegmental cholinergic nucleus isthmi pars parvocellularis (Ipc) from the optic tectum (OT) in barn owls by reversibly blocking excitatory transmission in the Ipc. Focal blockade in the Ipc decreases the gain and spatial discrimination of OT units specifically for the locations represented by the visual receptive fields (VRFs) of the disconnected Ipc units, and causes OT VRFs to shift away from that location. The results demonstrate mechanisms by which this cholinergic circuit controls bottom-up stimulus competition and by which top-down signals can bias this competition, and they establish causal linkages between a particular circuit, gain control and dynamic shifts of VRFs. This circuit may perform the same function in all vertebrate species.

  View details for DOI 10.1038/ncomms13472

  View details for Web of Science ID 000388180000001

  View details for PubMedID 27853140

• Selective disinhibition: A unified neural mechanism for predictive and post hoc attentional selection VISION RESEARCH Sridharan, D., Knudsen, E. I. 2015; 116: 194-209

  View details for DOI 10.1016/j.visres.2014.12.010

  View details for Web of Science ID 000364270400009

  View details for PubMedID 25542276

• Gamma oscillations in the midbrain spatial attention network: linking circuits to function CURRENT OPINION IN NEUROBIOLOGY Sridharan, D., Knudsen, E. I. 2015; 31: 189-198

  Abstract

  Gamma-band (25-140Hz) oscillations are ubiquitous in mammalian forebrain structures involved in sensory processing, attention, learning and memory. The optic tectum (OT) is the central structure in a midbrain network that participates critically in controlling spatial attention. In this review, we summarize recent advances in characterizing a neural circuit in this midbrain network that generates large amplitude, space-specific, gamma oscillations in the avian OT, both in vivo and in vitro. We describe key physiological and pharmacological mechanisms that produce and regulate the structure of these oscillations. The extensive similarities between midbrain gamma oscillations in birds and those in the neocortex and hippocampus of mammals, offer important insights into the functional significance of a midbrain gamma oscillatory code.

  View details for DOI 10.1016/j.conb.2014.11.006

  View details for Web of Science ID 000352680700028

  View details for PubMedID 25485519

• Cholinergic control of gamma power in the midbrain spatial attention network. journal of neuroscience Bryant, A. S., Goddard, C. A., Huguenard, J. R., Knudsen, E. I. 2015; 35 (2): 761-775

  Abstract

  The modulation of gamma power (25-90 Hz) is associated with attention and has been observed across species and brain areas. However, mechanisms that control these modulations are poorly understood. The midbrain spatial attention network in birds generates high-amplitude gamma oscillations in the local field potential that are thought to represent the highest priority location for attention. Here we explore, in midbrain slices from chickens, mechanisms that regulate the power of these oscillations, using high-resolution techniques including intracellular recordings from neurons targeted by calcium imaging. The results identify a specific subtype of neuron, expressing non-α7 nicotinic acetylcholine receptors, that directly drives inhibition in the gamma-generating circuit and switches the network into a primed state capable of producing high-amplitude oscillations. The special properties of this mechanism enable rapid, persistent changes in gamma power. The brain may employ this mechanism wherever rapid modulations of gamma power are critical to information processing.

  View details for DOI 10.1523/JNEUROSCI.4001-14.2015

  View details for PubMedID 25589769

• Descending Control of Neural Bias and Selectivity in a Spatial Attention Network: Rules and Mechanisms NEURON Mysore, S. P., Knudsen, E. I. 2014; 84 (1): 214-226

  View details for DOI 10.1016/j.neuron.2014.08.019

  View details for Web of Science ID 000342502800022

• Parallel Midbrain Microcircuits Perform Independent Temporal Transformations JOURNAL OF NEUROSCIENCE Goddard, C. A., Huguenard, J., Knudsen, E. 2014; 34 (24): 8130-8138

  Abstract

  The capacity to select the most important information and suppress distracting information is crucial for survival. The midbrain contains a network critical for the selection of the strongest stimulus for gaze and attention. In avians, the optic tectum (OT; called the superior colliculus in mammals) and the GABAergic nucleus isthmi pars magnocellularis (Imc) cooperate in the selection process. In the chicken, OT layer 10, located in intermediate layers, responds to afferent input with gamma periodicity (25-75 Hz), measured at the level of individual neurons and the local field potential. In contrast, Imc neurons, which receive excitatory input from layer 10 neurons, respond with tonic, unusually high discharge rates (>150 spikes/s). In this study, we reveal the source of this high-rate inhibitory activity: layer 10 neurons that project to the Imc possess specialized biophysical properties that enable them to transform afferent drive into high firing rates (∼130 spikes/s), whereas neighboring layer 10 neurons, which project elsewhere, transform afferent drive into lower-frequency, periodic discharge patterns. Thus, the intermediate layers of the OT contain parallel, intercalated microcircuits that generate different temporal patterns of activity linked to the functions of their respective downstream targets.

  View details for DOI 10.1523/JNEUROSCI.4399-13.2014

  View details for Web of Science ID 000338338700008

• Selective attention in birds. Current biology Sridharan, D., Schwarz, J. S., Knudsen, E. I. 2014; 24 (11): R510-3

  Abstract

  The natural world constantly inundates our senses with an abundance of information. Selective attention enables us to navigate this abundance intelligently by selecting the information that is most relevant, at each moment in time, for differential processing and decision-making. The attributes of attention have been studied in humans for over a century. In his influential 19(th) century treatise, The Principles of Psychology, philosopher and psychologist William James defined attention as: "… the taking possession by the mind, in clear and vivid form, of one out of what seem several simultaneously possible objects or trains of thought … It implies withdrawal from some things in order to deal effectively with others." (James, 1890). James' definition elegantly captures two key hallmarks of attention: the enhanced processing of task-relevant information (target information) and the suppression of task-irrelevant information (distracting information).

  View details for DOI 10.1016/j.cub.2013.12.046

  View details for PubMedID 24892907

• Visuospatial selective attention in chickens. Proceedings of the National Academy of Sciences of the United States of America Sridharan, D., Ramamurthy, D. L., Schwarz, J. S., Knudsen, E. I. 2014; 111 (19): E2056-65

  Abstract

  Voluntary control of attention promotes intelligent, adaptive behaviors by enabling the selective processing of information that is most relevant for making decisions. Despite extensive research on attention in primates, the capacity for selective attention in nonprimate species has never been quantified. Here we demonstrate selective attention in chickens by applying protocols that have been used to characterize visual spatial attention in primates. Chickens were trained to localize and report the vertical position of a target in the presence of task-relevant distracters. A spatial cue, the location of which varied across individual trials, indicated the horizontal, but not vertical, position of the upcoming target. Spatial cueing improved localization performance: accuracy (d') increased and reaction times decreased in a space-specific manner. Distracters severely impaired perceptual performance, and this impairment was greatly reduced by spatial cueing. Signal detection analysis with an "indecision" model demonstrated that spatial cueing significantly increased choice certainty in localizing targets. By contrast, error-aversion certainty (certainty of not making an error) remained essentially constant across cueing protocols, target contrasts, and individuals. The results show that chickens shift spatial attention rapidly and dynamically, following principles of stimulus selection that closely parallel those documented in primates. The findings suggest that the mechanisms that control attention have been conserved through evolution, and establish chickens-a highly visual species that is easily trained and amenable to cutting-edge experimental technologies-as an attractive model for linking behavior to neural mechanisms of selective attention.

  View details for DOI 10.1073/pnas.1316824111

  View details for PubMedID 24753566

• Spatially Reciprocal Inhibition of Inhibition within a Stimulus Selection Network in the Avian Midbrain. PloS one Goddard, C. A., Mysore, S. P., Bryant, A. S., Huguenard, J. R., Knudsen, E. I. 2014; 9 (1)

  View details for DOI 10.1371/journal.pone.0085865

  View details for PubMedID 24465755

• Distinguishing bias from sensitivity effects in multialternative detection tasks. J. Vision Sridharan, D., Steinmetze, N. A., Moore, T., Knudsen, E. I. 2014; 14 (9): 1-32
• Distinguishing bias from sensitivity effects in multialternative detection tasks. Journal of vision Sridharan, D., Steinmetz, N. A., Moore, T., Knudsen, E. I. 2014; 14 (9)

  View details for DOI 10.1167/14.9.16

  View details for PubMedID 25146574

• Distinguishing bias from sensitivity effects in multialternative detection tasks. Journal of vision Sridharan, D., Steinmetz, N. A., Moore, T., Knudsen, E. I. 2014; 14 (9)

  Abstract

  Studies investigating the neural bases of cognitive phenomena increasingly employ multialternative detection tasks that seek to measure the ability to detect a target stimulus or changes in some target feature (e.g., orientation or direction of motion) that could occur at one of many locations. In such tasks, it is essential to distinguish the behavioral and neural correlates of enhanced perceptual sensitivity from those of increased bias for a particular location or choice (choice bias). However, making such a distinction is not possible with established approaches. We present a new signal detection model that decouples the behavioral effects of choice bias from those of perceptual sensitivity in multialternative (change) detection tasks. By formulating the perceptual decision in a multidimensional decision space, our model quantifies the respective contributions of bias and sensitivity to multialternative behavioral choices. With a combination of analytical and numerical approaches, we demonstrate an optimal, one-to-one mapping between model parameters and choice probabilities even for tasks involving arbitrarily large numbers of alternatives. We validated the model with published data from two ternary choice experiments: a target-detection experiment and a length-discrimination experiment. The results of this validation provided novel insights into perceptual processes (sensory noise and competitive interactions) that can accurately and parsimoniously account for observers' behavior in each task. The model will find important application in identifying and interpreting the effects of behavioral manipulations (e.g., cueing attention) or neural perturbations (e.g., stimulation or inactivation) in a variety of multialternative tasks of perception, attention, and decision-making.

  View details for DOI 10.1167/14.9.16

  View details for PubMedID 25146574

• Spatial Probability Dynamically Modulates Visual Target Detection in Chickens PLOS ONE Sridharan, D., Ramamurthy, D. L., Knudsen, E. I. 2013; 8 (5)

  Abstract

  The natural world contains a rich and ever-changing landscape of sensory information. To survive, an organism must be able to flexibly and rapidly locate the most relevant sources of information at any time. Humans and non-human primates exploit regularities in the spatial distribution of relevant stimuli (targets) to improve detection at locations of high target probability. Is the ability to flexibly modify behavior based on visual experience unique to primates? Chickens (Gallus domesticus) were trained on a multiple alternative Go/NoGo task to detect a small, briefly-flashed dot (target) in each of the quadrants of the visual field. When targets were presented with equal probability (25%) in each quadrant, chickens exhibited a distinct advantage for detecting targets at lower, relative to upper, hemifield locations. Increasing the probability of presentation in the upper hemifield locations (to 80%) dramatically improved detection performance at these locations to be on par with lower hemifield performance. Finally, detection performance in the upper hemifield changed on a rapid timescale, improving with successive target detections, and declining with successive detections at the diagonally opposite location in the lower hemifield. These data indicate the action of a process that in chickens, as in primates, flexibly and dynamically modulates detection performance based on the spatial probabilities of sensory stimuli as well as on recent performance history.

  View details for DOI 10.1371/journal.pone.0064136

  View details for Web of Science ID 000319725500080

  View details for PubMedID 23734188

• A shared inhibitory circuit for both exogenous and endogenous control of stimulus selection NATURE NEUROSCIENCE Mysore, S. P., Knudsen, E. I. 2013; 16 (4): 473-U143

  Abstract

  The mechanisms by which the brain suppresses distracting stimuli to control the locus of attention are unknown. We found that focal, reversible inactivation of a single inhibitory circuit in the barn owl midbrain tegmentum, the nucleus isthmi pars magnocellularis (Imc), abolished both stimulus-driven (exogenous) and internally driven (endogenous) competitive interactions in the optic tectum (superior colliculus in mammals), which are vital to the selection of a target among distractors in behaving animals. Imc neurons transformed spatially precise multisensory and endogenous input into powerful inhibitory output that suppressed competing representations across the entire tectal space map. We identified a small, but highly potent, circuit that is employed by both exogenous and endogenous signals to exert competitive suppression in the midbrain selection network. Our findings reveal, to the best of our knowledge, for the first time, a neural mechanism for the construction of a priority map that is critical for the selection of the most important stimulus for gaze and attention.

  View details for DOI 10.1038/nn.3352

  View details for Web of Science ID 000316723700018

  View details for PubMedID 23475112

• Magnetic tracking of eye position in freely behaving chickens. Frontiers in systems neuroscience Schwarz, J. S., Sridharan, D., Knudsen, E. I. 2013; 7: 91-?

  Abstract

  Research on the visual system of non-primates, such as birds and rodents, is increasing. Evidence that neural responses can differ dramatically between head-immobilized and freely behaving animals underlines the importance of studying visual processing in ethologically relevant contexts. In order to systematically study visual responses in freely behaving animals, an unobtrusive system for monitoring eye-in-orbit position in real time is essential. We describe a novel system for monitoring eye position that utilizes a head-mounted magnetic displacement sensor coupled with an eye-implanted magnet. This system is small, lightweight, and offers high temporal and spatial resolution in real time. We use the system to demonstrate the stability of the eye and the stereotypy of eye position during two different behavioral tasks in chickens. This approach offers a viable alternative to search coil and optical eye tracking techniques for high resolution tracking of eye-in-orbit position in behaving animals.

  View details for DOI 10.3389/fnsys.2013.00091

  View details for PubMedID 24312023

• Gamma Oscillations Are Generated Locally in an Attention-Related Midbrain Network NEURON Goddard, C. A., Sridharan, D., Huguenard, J. R., Knudsen, E. I. 2012; 73 (3): 567-580

  Abstract

  Gamma-band (25-140 Hz) oscillations are a hallmark of sensory processing in the forebrain. The optic tectum (OT), a midbrain structure implicated in sensorimotor processing and attention, also exhibits gamma oscillations. However, the origin and mechanisms of these oscillations remain unknown. We discovered that in acute slices of the avian OT, persistent (>100 ms) epochs of large amplitude gamma oscillations can be evoked that closely resemble those recorded in vivo. We found that cholinergic, glutamatergic, and GABAergic mechanisms differentially regulate the structure of the oscillations at various timescales. These persistent oscillations originate in the multisensory layers of the OT and are broadcast to visual layers via the cholinergic nucleus Ipc, providing a potential mechanism for enhancing the processing of visual information within the OT. The finding that the midbrain contains an intrinsic gamma-generating circuit suggests that the OT could use its own oscillatory code to route signals to forebrain networks.

  View details for DOI 10.1016/j.neuron.2011.11.028

  View details for Web of Science ID 000300140600016

  View details for PubMedID 22325207

• Reciprocal Inhibition of Inhibition: A Circuit Motif for Flexible Categorization in Stimulus Selection NEURON Mysore, S. P., Knudsen, E. I. 2012; 73 (1): 193-205

  Abstract

  As a precursor to the selection of a stimulus for gaze and attention, a midbrain network categorizes stimuli into "strongest" and "others." The categorization tracks flexibly, in real time, the absolute strength of the strongest stimulus. In this study, we take a first-principles approach to computations that are essential for such categorization. We demonstrate that classical feedforward lateral inhibition cannot produce flexible categorization. However, circuits in which the strength of lateral inhibition varies with the relative strength of competing stimuli categorize successfully. One particular implementation--reciprocal inhibition of feedforward lateral inhibition--is structurally the simplest, and it outperforms others in flexibly categorizing rapidly and reliably. Strong predictions of this anatomically supported circuit model are validated by neural responses measured in the owl midbrain. The results demonstrate the extraordinary power of a remarkably simple, neurally grounded circuit motif in producing flexible categorization, a computation fundamental to attention, perception, and decision making.

  View details for DOI 10.1016/j.neuron.2011.10.037

  View details for Web of Science ID 000299446800018

  View details for PubMedID 22243757

• The role of a midbrain network in competitive stimulus selection CURRENT OPINION IN NEUROBIOLOGY Mysore, S. P., Knudsen, E. I. 2011; 21 (4): 653-660

  Abstract

  A midbrain network interacts with the well-known frontoparietal forebrain network to select stimuli for gaze and spatial attention. The midbrain network, containing the superior colliculus (SC; optic tectum, OT, in non-mammalian vertebrates) and the isthmic nuclei, helps evaluate the relative priorities of competing stimuli and encodes them in a topographic map of space. Behavioral experiments in monkeys demonstrate an essential contribution of the SC to stimulus selection when the relative priorities of competing stimuli are similar. Neurophysiological results from the owl OT demonstrate a neural correlate of this essential contribution of the SC/OT. The multi-layered, spatiotopic organization of the midbrain network lends itself to the analysis and modeling of the mechanisms underlying stimulus selection for gaze and spatial attention.

  View details for DOI 10.1016/j.conb.2011.05.024

  View details for Web of Science ID 000295660500020

  View details for PubMedID 21696945

• Control from below: the role of a midbrain network in spatial attention EUROPEAN JOURNAL OF NEUROSCIENCE Knudsen, E. I. 2011; 33 (11): 1961-1972

  Abstract

  Spatial attention enables the brain to analyse and evaluate information selectively from a specific location in space, a capacity essential for any animal to behave adaptively in a complex world. We usually think of spatial attention as being controlled by a frontoparietal network in the forebrain. However, emerging evidence shows that a midbrain network also plays a critical role in controlling spatial attention. Moreover, the highly differentiated, retinotopic organization of the midbrain network, especially in birds, makes it amenable to detailed analysis with modern techniques that can elucidate circuit, cellular and synaptic mechanisms of attention. The following review discusses the role of the midbrain network in controlling attention, the neural circuits that support this role and current knowledge about the computations performed by these circuits.

  View details for DOI 10.1111/j.1460-9568.2011.07696.x

  View details for Web of Science ID 000291400300004

  View details for PubMedID 21645092

• Flexible Categorization of Relative Stimulus Strength by the Optic Tectum JOURNAL OF NEUROSCIENCE Mysore, S. P., Knudsen, E. I. 2011; 31 (21): 7745-7752

  Abstract

  Categorization is the process by which the brain segregates continuously variable stimuli into discrete groups. We report that patterns of neural population activity in the owl optic tectum (OT) categorize stimuli based on their relative strengths into "strongest" versus "other." The category boundary shifts adaptively to track changes in the absolute strength of the strongest stimulus. This population-wide categorization is mediated by the responses of a small subset of neurons. Our data constitute the first direct demonstration of explicit categorization of stimuli by a neural network based on relative stimulus strength or salience. The finding of categorization by the population code relaxes constraints on the properties of downstream decoders that might read out the location of the strongest stimulus. These results indicate that the ensemble neural code in the OT could mediate bottom-up stimulus selection for gaze and attention, a form of stimulus categorization in which the category boundary often shifts within hundreds of milliseconds.

  View details for DOI 10.1523/JNEUROSCI.5425-10.2011

  View details for Web of Science ID 000290956400016

  View details for PubMedID 21613487

• Space coding by gamma oscillations in the barn owl optic tectum JOURNAL OF NEUROPHYSIOLOGY Sridharan, D., Boahen, K., Knudsen, E. I. 2011; 105 (5): 2005-2017

  Abstract

  Gamma-band (25-140 Hz) oscillations of the local field potential (LFP) are evoked by sensory stimuli in the mammalian forebrain and may be strongly modulated in amplitude when animals attend to these stimuli. The optic tectum (OT) is a midbrain structure known to contribute to multimodal sensory processing, gaze control, and attention. We found that presentation of spatially localized stimuli, either visual or auditory, evoked robust gamma oscillations with distinctive properties in the superficial (visual) layers and in the deep (multimodal) layers of the owl's OT. Across layers, gamma power was tuned sharply for stimulus location and represented space topographically. In the superficial layers, induced LFP power peaked strongly in the low-gamma band (25-90 Hz) and increased gradually with visual contrast across a wide range of contrasts. Spikes recorded in these layers included presumptive axonal (input) spikes that encoded stimulus properties nearly identically with gamma oscillations and were tightly phase locked with the oscillations, suggesting that they contribute to the LFP oscillations. In the deep layers, induced LFP power was distributed across the low and high (90-140 Hz) gamma-bands and tended to reach its maximum value at relatively low visual contrasts. In these layers, gamma power was more sharply tuned for stimulus location, on average, than were somatic spike rates, and somatic spikes synchronized with gamma oscillations. Such gamma synchronized discharges of deep-layer neurons could provide a high-resolution temporal code for signaling the location of salient sensory stimuli.

  View details for DOI 10.1152/jn.00965.2010

  View details for Web of Science ID 000290710300006

  View details for PubMedID 21325681

• Rules of Competitive Stimulus Selection in a Cholinergic Isthmic Nucleus of the Owl Midbrain JOURNAL OF NEUROSCIENCE Asadollahi, A., Mysore, S. P., Knudsen, E. I. 2011; 31 (16): 6088-6097

  Abstract

  In a natural scene, multiple stimuli compete for the control of gaze direction and attention. The nucleus isthmi pars parvocellularis (Ipc) is a cholinergic, midbrain nucleus that is reciprocally interconnected to the optic tectum, a structure known to be involved in the control of gaze and attention. Previous research has shown that the responses of many Ipc units to a visual stimulus presented inside the classical receptive field (RF) can be powerfully inhibited when the strength of a distant, competing stimulus becomes the stronger stimulus. This study investigated further the nature of competitive interactions in the Ipc of owls by using two complementary protocols: in the first protocol, we measured the effects of a distant stimulus on responses to an RF stimulus located at different positions inside the RF; in the second protocol, we measured the effects of a distant stimulus on responses to RF stimuli of different strengths. The first protocol demonstrated that the effect of a competing stimulus is purely divisive: the competitor caused a proportional reduction in responses to the RF stimulus that did not alter either the location or sharpness of spatial tuning. The second protocol demonstrated that, for most units, the strength of this divisive inhibition is regulated powerfully by the relative strengths of the competing stimuli: inhibition was strong when the competitor was the stronger stimulus and weak when the competitor was the weaker stimulus. The data indicate that competitive interactions in the Ipc depend on feedback and a globally divisive inhibitory network.

  View details for DOI 10.1523/JNEUROSCI.0023-11.2011

  View details for Web of Science ID 000289769400023

  View details for PubMedID 21508234

• Signaling of the Strongest Stimulus in the Owl Optic Tectum JOURNAL OF NEUROSCIENCE Mysore, S. P., Asadollahi, A., Knudsen, E. I. 2011; 31 (14): 5186-5196

  Abstract

  Essential to the selection of the next target for gaze or attention is the ability to compare the strengths of multiple competing stimuli (bottom-up information) and to signal the strongest one. Although the optic tectum (OT) has been causally implicated in stimulus selection, how it computes the strongest stimulus is unknown. Here, we demonstrate that OT neurons in the barn owl systematically encode the relative strengths of simultaneously occurring stimuli independently of sensory modality. Moreover, special "switch-like" responses of a subset of neurons abruptly increase when the stimulus inside their receptive field becomes the strongest one. Such responses are not predicted by responses to single stimuli and, indeed, are eliminated in the absence of competitive interactions. We demonstrate that this sensory transformation substantially boosts the representation of the strongest stimulus by creating a binary discrimination signal, thereby setting the stage for potential winner-take-all target selection for gaze and attention.

  View details for DOI 10.1523/JNEUROSCI.4592-10.2011

  View details for Web of Science ID 000289213500003

  View details for PubMedID 21471353

• Stimulus-driven competition in a cholinergic midbrain nucleus NATURE NEUROSCIENCE Asadollahi, A., Mysore, S. P., Knudsen, E. I. 2010; 13 (7): 889-U138

  Abstract

  The mechanisms by which the brain selects a particular stimulus as the next target for gaze are poorly understood. A cholinergic nucleus in the owl's midbrain exhibits functional properties that suggest its role in bottom-up stimulus selection. Neurons in the nucleus isthmi pars parvocellularis (Ipc) responded to wide ranges of visual and auditory features, but they were not tuned to particular values of those features. Instead, they encoded the relative strengths of stimuli across the entirety of space. Many neurons exhibited switch-like properties, abruptly increasing their responses to a stimulus in their receptive field when it became the strongest stimulus. This information propagates directly to the optic tectum, a structure involved in gaze control and stimulus selection, as periodic (25-50 Hz) bursts of cholinergic activity. The functional properties of Ipc neurons resembled those of a salience map, a core component in computational models for spatial attention and gaze control.

  View details for DOI 10.1038/nn.2573

  View details for Web of Science ID 000279173900023

  View details for PubMedID 20526331

• A Dominance Hierarchy of Auditory Spatial Cues in Barn Owls PLOS ONE Witten, I. B., Knudsen, P. F., Knudsen, E. I. 2010; 5 (4)

  Abstract

  Barn owls integrate spatial information across frequency channels to localize sounds in space.We presented barn owls with synchronous sounds that contained different bands of frequencies (3-5 kHz and 7-9 kHz) from different locations in space. When the owls were confronted with the conflicting localization cues from two synchronous sounds of equal level, their orienting responses were dominated by one of the sounds: they oriented toward the location of the low frequency sound when the sources were separated in azimuth; in contrast, they oriented toward the location of the high frequency sound when the sources were separated in elevation. We identified neural correlates of this behavioral effect in the optic tectum (OT, superior colliculus in mammals), which contains a map of auditory space and is involved in generating orienting movements to sounds. We found that low frequency cues dominate the representation of sound azimuth in the OT space map, whereas high frequency cues dominate the representation of sound elevation.Significance: We argue that the dominance hierarchy of localization cues reflects several factors: 1) the relative amplitude of the sound providing the cue, 2) the resolution with which the auditory system measures the value of a cue, and 3) the spatial ambiguity in interpreting the cue. These same factors may contribute to the relative weighting of sound localization cues in other species, including humans.

  View details for DOI 10.1371/journal.pone.0010396

  View details for Web of Science ID 000277154200028

  View details for PubMedID 20442852

• Global Inhibition and Stimulus Competition in the Owl Optic Tectum JOURNAL OF NEUROSCIENCE Mysore, S. P., Asadollahi, A., Knudsen, E. I. 2010; 30 (5): 1727-1738

  Abstract

  Stimulus selection for gaze and spatial attention involves competition among stimuli across sensory modalities and across all of space. We demonstrate that such cross-modal, global competition takes place in the intermediate and deep layers of the optic tectum, a structure known to be involved in gaze control and attention. A variety of either visual or auditory stimuli located anywhere outside of a neuron's receptive field (RF) were shown to suppress or completely eliminate responses to a visual stimulus located inside the RF in nitrous oxide sedated owls. The essential mechanism underlying this stimulus competition is global, divisive inhibition. Unlike the effect of the classical inhibitory surround, which decreases with distance from the RF center and shapes neuronal responses to individual stimuli, global inhibition acts across the entirety of space and modulates responses primarily in the context of multiple stimuli. Whereas the source of this global inhibition is as yet unknown, our data indicate that different networks mediate the classical surround and global inhibition. We hypothesize that this global, cross-modal inhibition, which acts automatically in a bottom-up manner even in sedated animals, is critical to the creation of a map of stimulus salience in the optic tectum.

  View details for DOI 10.1523/JNEUROSCI.3740-09.2010

  View details for Web of Science ID 000274246700016

  View details for PubMedID 20130182

• Visual Modulation of Auditory Responses in the Owl Inferior Colliculus JOURNAL OF NEUROPHYSIOLOGY Bergan, J. F., Knudsen, E. I. 2009; 101 (6): 2924-2933

  Abstract

  The barn owl's central auditory system creates a map of auditory space in the external nucleus of the inferior colliculus (ICX). Although the crucial role visual experience plays in the formation and maintenance of this auditory space map is well established, the mechanism by which vision influences ICX responses remains unclear. Surprisingly, previous experiments have found that in the absence of extensive pharmacological manipulation, visual stimuli do not drive neural responses in the ICX. Here we investigated the influence of dynamic visual stimuli on auditory responses in the ICX. We show that a salient visual stimulus, when coincident with an auditory stimulus, can modulate auditory responses in the ICX even though the same visual stimulus may elicit no neural responses when presented alone. For each ICX neuron, the most effective auditory and visual stimuli were located in the same region of space. In addition, the magnitude of the visual modulation of auditory responses was dependent on the context of the stimulus presentation with novel visual stimuli eliciting consistently larger response modulations than frequently presented visual stimuli. Thus the visual modulation of ICX responses is dependent on the characteristics of the visual stimulus as well as on the spatial and temporal correspondence of the auditory and visual stimuli. These results demonstrate moment-to-moment visual enhancements of auditory responsiveness that, in the short-term, increase auditory responses to salient bimodal stimuli and in the long-term could serve to instruct the adaptive auditory plasticity necessary to maintain accurate auditory orienting behavior.

  View details for DOI 10.1152/jn.91313.2008

  View details for Web of Science ID 000266398500019

  View details for PubMedID 19321633

• Distinct Mechanisms for Top-Down Control of Neural Gain and Sensitivity in the Owl Optic Tectum NEURON Winkowski, D. E., Knudsen, E. I. 2008; 60 (4): 698-708

  Abstract

  We demonstrate that distinct mechanisms of top-down control regulate, respectively, the sensitivity and gain of sensory responses in the owl's optic tectum (OT). Electrical microstimulation in the forebrain gaze control area, the arcopallial gaze field (AGF), results in a space-specific regulation of sensory responses in the OT. AGF microstimulation increases the responsiveness of OT neurons representing stimuli at the same location as that represented at the AGF site. We show that the mechanism that underlies this effect operates focally to enhance neuronal sensitivity and improve tuning consistency and spatial resolution. At the same time, AGF microstimulation decreases the responsiveness of OT neurons representing stimuli at all other locations. The mechanism that underlies this effect operates globally to modulate neuronal gain. The coordinated action of these different mechanisms can account for many of the reported effects of spatial attention on neural responses in monkeys and on behavioral performance in humans.

  View details for DOI 10.1016/j.neuron.2008.09.013

  View details for Web of Science ID 000261603200018

  View details for PubMedID 19038225

• A Hebbian learning rule mediates asymmetric plasticity in aligning sensory representations JOURNAL OF NEUROPHYSIOLOGY Witten, I. B., Knudsen, E. I., Sompolinsky, H. 2008; 100 (2): 1067-1079

  Abstract

  In the brain, mutual spatial alignment across different sensory representations can be shaped and maintained through plasticity. Here, we use a Hebbian model to account for the synaptic plasticity that results from a displacement of the space representation for one input channel relative to that of another, when the synapses from both channels are equally plastic. Surprisingly, although the synaptic weights for the two channels obeyed the same Hebbian learning rule, the amount of plasticity exhibited by the respective channels was highly asymmetric and depended on the relative strength and width of the receptive fields (RFs): the channel with the weaker or broader RFs always exhibited most or all of the plasticity. A fundamental difference between our Hebbian model and most previous models is that in our model synaptic weights were normalized separately for each input channel, ensuring that the circuit would respond to both sensory inputs. The model produced three distinct regimes of plasticity dynamics (winner-take-all, mixed-shift, and no-shift), with the transition between the regimes depending on the size of the spatial displacement and the degree of correlation between the sensory channels. In agreement with experimental observations, plasticity was enhanced by the accumulation of incremental adaptive adjustments to a sequence of small displacements. These same principles would apply not only to the maintenance of spatial registry across input channels, but also to the experience-dependent emergence of aligned representations in developing circuits.

  View details for DOI 10.1152/jn.00013.2008

  View details for Web of Science ID 000258394500046

  View details for PubMedID 18525023

• Intrinsic excitability of cholinergic neurons in the rat parabigeminal nucleus JOURNAL OF NEUROPHYSIOLOGY Goddard, C. A., Knudsen, E. I., Huguenard, J. R. 2007; 98 (6): 3486-3493

  Abstract

  Cholinergic neurons in the parabigeminal nucleus of the rat midbrain were studied in an acute slice preparation. Spontaneous, regular action potentials were observed both with cell-attached patch recordings as well as with whole cell current-clamp recordings. The spontaneous activity of parabigeminal nucleus (PBN) neurons was not due to synaptic input as it persisted in the presence of the pan-ionotropic excitatory neurotransmitter receptor blocker, kynurenic acid, and the cholinergic blockers dihydro-beta-erythroidine (DHbetaE) and atropine. This result suggests the existence of intrinsic currents that enable spontaneous activity. In voltage-clamp recordings, I(H) and I(A) currents were observed in most PBN neurons. I(A) had voltage-dependent features that would permit it to contribute to spontaneous firing. In contrast, I(H) was significantly activated at membrane potentials lower than the trough of the spike afterhyperpolarization, suggesting that I(H) does not contribute to spontaneous firing of PBN neurons. Consistent with this interpretation, application of 25 microM ZD-7288, which blocked I(H), did not affect the rate of spontaneous firing in PBN neurons. Counterparts to I(A) and I(H) were observed in current-clamp recordings: I(A) was reflected as a slow voltage ramp observed between action potentials and on release from hyperpolarization, and I(H) was reflected as a depolarizing sag often accompanied by rebound spikes in response to hyperpolarizing current injections. In response to depolarizing current injections, PBN neurons fired at high frequencies, with relatively little accommodation. Ultimately, the spontaneous activity in PBN neurons could be used to modulate cholinergic drive in the superior colliculus in either positive or negative directions.

  View details for DOI 10.1152/jn.00960.2007

  View details for Web of Science ID 000251775700033

  View details for PubMedID 17898138

• Top-down control of Multimodal sensitivity in the barn owl optic tectum JOURNAL OF NEUROSCIENCE Winkowski, D. E., Knudsen, E. I. 2007; 27 (48): 13279-13291

  Abstract

  We studied the effects of electrically microstimulating a gaze-control area in the owl's forebrain, the arcopallial gaze fields (AGFs), on the responsiveness of neurons in the optic tectum (OT) to visual and auditory stimuli. Microstimulation of the AGF enhanced the visual and auditory responsiveness and stimulus discriminability of OT neurons representing the same location in space as that represented at the microstimulation site in the AGF. At such OT sites, AGF microstimulation also sharpened auditory receptive fields and shifted them toward the location represented at the AGF stimulation site. At the same time, AGF microstimulation suppressed the responsiveness of OT neurons that represented visual or auditory stimuli at other locations in space. The top-down influences of this forebrain gaze-control area on sensory responsiveness in the owl OT are strikingly similar to the space-specific regulation of visual responsiveness in the monkey visual cortex produced by voluntary attention as well as by microstimulation of the frontal eye fields. This experimental approach provides a means for discovering mechanisms that underlie the top-down regulation of sensory responses.

  View details for DOI 10.1523/JNEUROSCI.3937-07.2007

  View details for Web of Science ID 000251296700025

  View details for PubMedID 18045922

• Adaptive auditory plasticity in developing and adult animals PROGRESS IN NEUROBIOLOGY Keuroghlian, A. S., Knudsen, E. I. 2007; 82 (3): 109-121

  Abstract

  Enormous progress has been made in our understanding of adaptive plasticity in the central auditory system. Experiments on a range of species demonstrate that, in adults, the animal must attend to (i.e., respond to) a stimulus in order for plasticity to be induced, and the plasticity that is induced is specific for the acoustic feature to which the animal has attended. The requirement that an adult animal must attend to a stimulus in order for adaptive plasticity to occur suggests an essential role of neuromodulatory systems in gating plasticity in adults. Indeed, neuromodulators, particularly acetylcholine (ACh), that are associated with the processes of attention, have been shown to enable adaptive plasticity in adults. In juvenile animals, attention may facilitate plasticity, but it is not always required: during sensitive periods, mere exposure of an animal to an atypical auditory environment can result in large functional changes in certain auditory circuits. Thus, in both the developing and mature auditory systems substantial experience-dependent plasticity can occur, but the conditions under which it occurs are far more stringent in adults. We review experimental results that demonstrate experience-dependent plasticity in the central auditory representations of sound frequency, level and temporal sequence, as well as in the representations of binaural localization cues in both developing and adult animals.

  View details for DOI 10.1016/j.pneurobio.2007.03.005

  View details for Web of Science ID 000247741000001

  View details for PubMedID 17493738

• Fundamental components of attention ANNUAL REVIEW OF NEUROSCIENCE Knudsen, E. I. 2007; 30: 57-78

  Abstract

  A mechanistic understanding of attention is necessary for the elucidation of the neurobiological basis of conscious experience. This chapter presents a framework for thinking about attention that facilitates the analysis of this cognitive process in terms of underlying neural mechanisms. Four processes are fundamental to attention: working memory, top-down sensitivity control, competitive selection, and automatic bottom-up filtering for salient stimuli. Each process makes a distinct and essential contribution to attention. Voluntary control of attention involves the first three processes (working memory, top-down sensitivity control, and competitive selection) operating in a recurrent loop. Recent results from neurobiological research on attention are discussed within this framework.

  View details for DOI 10.1146/annurev.neuro.30.051606.094256

  View details for Web of Science ID 000248735400003

  View details for PubMedID 17417935

• Auditory and visual space maps in the cholinergic nucleus isthmi pars parvocellularis of the barn owl JOURNAL OF NEUROSCIENCE Maczko, K. A., Knudsen, P. F., Knudsen, E. I. 2006; 26 (49): 12799-12806

  Abstract

  The nucleus isthmi pars parvocellularis (Ipc) is a midbrain cholinergic nucleus that shares reciprocal, topographic connections with the optic tectum (OT). Ipc neurons project to spatially restricted columns in the OT, contacting essentially all OT layers in a given column. Previous research characterizes the Ipc as a visual processor. We found that, in the barn owl, the Ipc responds to auditory as well as to visual stimuli. Auditory responses were tuned broadly for frequency, but sharply for spatial cues. We measured the tuning of Ipc units to binaural sound localization cues, including interaural timing differences (ITDs) and interaural level differences (ILDs). Units in the Ipc were tuned to specific values of both ITD and ILD and were organized systematically according to their ITD and ILD tuning, forming a map of space. The auditory space map aligned with the visual space map in the Ipc. These results demonstrate that the Ipc encodes the spatial location of objects, independent of stimulus modality. These findings, combined with the precise pattern of projections from the Ipc to the OT, suggest that the role of the Ipc is to regulate the sensitivity of OT neurons in a space-specific manner.

  View details for DOI 10.1523/JNEUROSCI.3946-06.2006

  View details for Web of Science ID 000242626100020

  View details for PubMedID 17151283

• Dynamic shifts in the owl's auditory space map predict moving sound location NATURE NEUROSCIENCE Witten, I. B., Bergan, J. F., Knudsen, E. I. 2006; 9 (11): 1439-1445

  Abstract

  The optic tectum of the barn owl contains a map of auditory space. We found that, in response to moving sounds, the locations of receptive fields that make up the map shifted toward the approaching sound. The magnitude of the receptive field shifts increased systematically with increasing stimulus velocity and, therefore, was appropriate to compensate for sensory and motor delays inherent to auditory orienting behavior. Thus, the auditory space map is not static, but shifts adaptively and dynamically in response to stimulus motion. We provide a computational model to account for these results. Because the model derives predictive responses from processes that are known to occur commonly in neural networks, we hypothesize that analogous predictive responses will be found to exist widely in the central nervous system. This hypothesis is consistent with perceptions of stimulus motion in humans for many sensory parameters.

  View details for DOI 10.1038/nn1781

  View details for Web of Science ID 000242403800023

  View details for PubMedID 17013379

• Adaptation in the auditory space map of the barn owl JOURNAL OF NEUROPHYSIOLOGY Gutfreund, Y., Knudsen, E. I. 2006; 96 (2): 813-825

  Abstract

  Auditory neurons in the owl's external nucleus of the inferior colliculus (ICX) integrate information across frequency channels to create a map of auditory space. This study describes a powerful, sound-driven adaptation of unit responsiveness in the ICX and explores the implications of this adaptation for sensory processing. Adaptation in the ICX was analyzed by presenting lightly anesthetized owls with sequential pairs of dichotic noise bursts. Adaptation occurred in response even to weak, threshold-level sounds and remained strong for more than 100 ms after stimulus offset. Stimulation by one range of sound frequencies caused adaptation that generalized across the entire broad range of frequencies to which these units responded. Identical stimuli were used to test adaptation in the lateral shell of the central nucleus of the inferior colliculus (ICCls), which provides input directly to the ICX. Compared with ICX adaptation, adaptation in the ICCls was substantially weaker, shorter lasting, and far more frequency specific, suggesting that part of the adaptation observed in the ICX was attributable to processes resident to the ICX. The sharp tuning of ICX neurons to space, along with their broad tuning to frequency, allows ICX adaptation to preserve a representation of stimulus location, regardless of the frequency content of the sound. The ICX is known to be a site of visually guided auditory map plasticity. ICX adaptation could play a role in this cross-modal plasticity by providing a short-term memory of the representation of auditory localization cues that could be compared with later-arriving, visual-spatial information from bimodal stimuli.

  View details for DOI 10.1152/jn.01144.2005

  View details for Web of Science ID 000238974700031

  View details for PubMedID 16707713

• Economic, neurobiological, and behavioral perspectives on building America's future workforce PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Knudsen, E. I., Heckman, J. J., Cameron, J. L., Shonkoff, J. P. 2006; 103 (27): 10155-10162

  Abstract

  A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills and on brain architecture and neurochemistry, that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions, and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years.

  View details for DOI 10.1073/pnas.0600888103

  View details for Web of Science ID 000239069400003

  View details for PubMedID 16801553

• Top-down gain control of the auditory space map by gaze control circuitry in the barn owl NATURE Winkowski, D. E., Knudsen, E. I. 2006; 439 (7074): 336-339

  Abstract

  High-level circuits in the brain that control the direction of gaze are intimately linked with the control of visual spatial attention. Immediately before an animal directs its gaze towards a stimulus, both psychophysical sensitivity to that visual stimulus and the responsiveness of high-order neurons in the cerebral cortex that represent the stimulus increase dramatically. Equivalent effects on behavioural sensitivity and neuronal responsiveness to visual stimuli result from focal electrical microstimulation of gaze control centres in monkeys. Whether the gaze control system modulates neuronal responsiveness in sensory modalities other than vision is unknown. Here we show that electrical microstimulation applied to gaze control circuitry in the forebrain of barn owls regulates the gain of midbrain auditory responses in an attention-like manner. When the forebrain circuit was activated, midbrain responses to auditory stimuli at the location encoded by the forebrain site were enhanced and spatial selectivity was sharpened. The same stimulation suppressed responses to auditory stimuli represented at other locations in the midbrain map. Such space-specific, top-down regulation of auditory responses by gaze control circuitry in the barn owl suggests that the central nervous system uses a common strategy for dynamically regulating sensory gain that applies across modalities, brain areas and classes of vertebrate species. This approach provides a path for discovering mechanisms that underlie top-down gain control in the central nervous system.

  View details for DOI 10.1038/nature04411

  View details for Web of Science ID 000234682100045

  View details for PubMedID 16421572

• Auditory-visual fusion in speech perception in children with cochlear implants PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Schorr, E. A., Fox, N. A., Van Wassenhove, V., Knudsen, E. I. 2005; 102 (51): 18748-18750

  Abstract

  Speech, for most of us, is a bimodal percept whenever we both hear the voice and see the lip movements of a speaker. Children who are born deaf never have this bimodal experience. We tested children who had been deaf from birth and who subsequently received cochlear implants for their ability to fuse the auditory information provided by their implants with visual information about lip movements for speech perception. For most of the children with implants (92%), perception was dominated by vision when visual and auditory speech information conflicted. For some, bimodal fusion was strong and consistent, demonstrating a remarkable plasticity in their ability to form auditory-visual associations despite the atypical stimulation provided by implants. The likelihood of consistent auditory-visual fusion declined with age at implant beyond 2.5 years, suggesting a sensitive period for bimodal integration in speech perception.

  View details for DOI 10.1073/pnas.0508862102

  View details for Web of Science ID 000234174300089

  View details for PubMedID 16339316

• Why seeing is believing: Merging auditory and visual worlds NEURON Witten, I. B., Knudsen, E. I. 2005; 48 (3): 489-496

  Abstract

  Vision may dominate our perception of space not because of any inherent physiological advantage of visual over other sensory connections in the brain, but because visual information tends to be more reliable than other sources of spatial information, and the central nervous system integrates information in a statistically optimal fashion. This review discusses recent experiments on audiovisual integration that support this hypothesis. We consider candidate neural codes that would enable optimal integration and the implications of optimal integration for perception and plasticity.

  View details for DOI 10.1016/j.neuron.2005.10.020

  View details for Web of Science ID 000233250100009

  View details for PubMedID 16269365

• Hunting increases adaptive auditory map plasticity in adult barn owls JOURNAL OF NEUROSCIENCE Bergan, J. F., Ro, P., Ro, D., Knudsen, E. I. 2005; 25 (42): 9816-9820

  Abstract

  The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.

  View details for DOI 10.1523/JNEUROSCI.2533-05.2005

  View details for Web of Science ID 000232669300026

  View details for PubMedID 16237185

• Anatomical traces of juvenile learning in the auditory system of adult barn owls NATURE NEUROSCIENCE Linkenhoker, B. A., von der Ohe, C. G., Knudsen, E. I. 2005; 8 (1): 93-98

  Abstract

  Early experience plays a powerful role in shaping adult neural circuitry and behavior. In barn owls, early experience markedly influences sound localization. Juvenile owls that learn new, abnormal associations between auditory cues and locations in visual space as a result of abnormal visual experience can readapt to the same abnormal experience in adulthood, when plasticity is otherwise limited. Here we show that abnormal anatomical projections acquired during early abnormal sensory experience persist long after normal experience has been restored. These persistent projections are perfectly situated to provide a physical framework for subsequent readaptation in adulthood to the abnormal sensory conditions experienced in early life. Our results show that anatomical changes that support strong learned neural connections early in life can persist even after they are no longer functionally expressed. This maintenance of silenced neural circuitry that was once adaptive may represent an important mechanism by which the brain preserves a record of early experience.

  View details for DOI 10.1038/nn1367

  View details for Web of Science ID 000225967600021

  View details for PubMedID 15608636

• Sensitive periods in the development of the brain and behavior JOURNAL OF COGNITIVE NEUROSCIENCE Knudsen, E. I. 2004; 16 (8): 1412-1425

  Abstract

  Experience exerts a profound influence on the brain and, therefore, on behavior. When the effect of experience on the brain is particularly strong during a limited period in development, this period is referred to as a sensitive period. Such periods allow experience to instruct neural circuits to process or represent information in a way that is adaptive for the individual. When experience provides information that is essential for normal development and alters performance permanently, such sensitive periods are referred to as critical periods. Although sensitive periods are reflected in behavior, they are actually a property of neural circuits. Mechanisms of plasticity at the circuit level are discussed that have been shown to operate during sensitive periods. A hypothesis is proposed that experience during a sensitive period modifies the architecture of a circuit in fundamental ways, causing certain patterns of connectivity to become highly stable and, therefore, energetically preferred. Plasticity that occurs beyond the end of a sensitive period, which is substantial in many circuits, alters connectivity patterns within the architectural constraints established during the sensitive period. Preferences in a circuit that result from experience during sensitive periods are illustrated graphically as changes in a ''stability landscape,'' a metaphor that represents the relative contributions of genetic and experiential influences in shaping the information processing capabilities of a neural circuit. By understanding sensitive periods at the circuit level, as well as understanding the relationship between circuit properties and behavior, we gain a deeper insight into the critical role that experience plays in shaping the development of the brain and behavior.

  View details for Web of Science ID 000224738000009

  View details for PubMedID 15509387

• Multiple sites of adaptive plasticity in the owl's auditory localization pathway JOURNAL OF NEUROSCIENCE DeBello, W. M., Knudsen, E. I. 2004; 24 (31): 6853-6861

  Abstract

  In the midbrain auditory localization pathway of the barn owl, a map of auditory space is relayed from the external nucleus of the inferior colliculus (ICX) to the deep and intermediate layers of the optic tectum (OT) and from these layers to the superficial layers. Within the OT, the auditory space map aligns with a visual map of space. Raising young barn owls with a prismatic displacement of the visual field leads to progressive changes in auditory tuning in the OT that tend to realign the auditory space map with the prismatically displaced visual space map. The only known site of this adaptive plasticity is in the ICX, in which the auditory system first creates a map of space. In this study, we identified an additional site of plasticity in the OT. In owls that experienced prisms beginning late in the juvenile period, adaptive shifts in auditory tuning in the superficial layers of the OT exceeded the adaptive shifts that occurred in the deep layers of the OT or in the ICX. Anatomical results from these owls demonstrated that the topography of intrinsic OT connections was systematically altered in the adaptive direction. In juvenile owls, plasticity in the OT increased as plasticity in the ICX decreased. Because plasticity at both sites has been shown to decline substantially in adults, these results suggest that an age-dependent decrease in auditory map plasticity occurs first in the ICX and later at the higher level, in the OT.

  View details for DOI 10.1523/JNEUROSCI.0480-04.2004

  View details for Web of Science ID 000223102500001

  View details for PubMedID 15295019

• Adaptive plasticity in the auditory thalamus of juvenile barn owls JOURNAL OF NEUROSCIENCE Miller, G. L., Knudsen, E. I. 2003; 23 (3): 1059-1065

  Abstract

  Little is known about the capacity of the thalamus for experience-dependent plasticity. Here, we demonstrate adaptive changes in the tuning of auditory thalamic neurons to a major category of sound localization cue, interaural time differences (ITDs), in juvenile barn owls that experience chronic abnormal hearing. Abnormal hearing was caused by a passive acoustic filtering device implanted in one ear that altered the timing and level of sound differently at different frequencies. Experience with this device resulted in adaptive, frequency-dependent shifts in the tuning of thalamic neurons to ITD that mimicked the acoustic effects of the device. Abnormal hearing did not alter ITD tuning in the central nucleus of the inferior colliculus, the primary source of input to the auditory thalamus. Therefore, the thalamus is the earliest stage in the forebrain pathway in which this plasticity is expressed. A visual manipulation, chronic prismatic displacement of the visual field, which causes adaptive changes in ITD tuning at higher levels in the forebrain, had no effect on thalamic ITD tuning. The results demonstrate that, during the juvenile period, auditory experience shapes neuronal response properties in the thalamus in a frequency-specific manner and suggest that this thalamic plasticity is driven by self-organizational forces and not by visual instruction.

  View details for Web of Science ID 000180865400038

  View details for PubMedID 12574436

• Incremental training increases the plasticity of the auditory space map in adult barn owls NATURE Linkenhoker, B. A., Knudsen, E. I. 2002; 419 (6904): 293-296

  Abstract

  The plasticity in the central nervous system that underlies learning is generally more restricted in adults than in young animals. In one well-studied example, the auditory localization pathway has been shown to be far more limited in its capacity to adjust to abnormal experience in adult than in juvenile barn owls. Plasticity in this pathway has been induced by exposing owls to prismatic spectacles that cause a large, horizontal shift of the visual field. With prisms, juveniles learn new associations between auditory cues, such as interaural time difference (ITD), and locations in visual space, and acquire new neurophysiological maps of ITD in the optic tectum, whereas adults do neither. Here we show that when the prismatic shift is experienced in small increments, maps of ITD in adults do change adaptively. Once established through incremental training, new ITD maps can be reacquired with a single large prismatic shift. Our results show that there is a substantially greater capacity for plasticity in adults than was previously recognized and highlight a principled strategy for tapping this capacity that could be applied in other areas of the adult central nervous system.

  View details for Web of Science ID 000178056300044

  View details for PubMedID 12239566

• Gated visual input to the central auditory system SCIENCE Gutfreund, Y., Zheng, W. M., Knudsen, E. I. 2002; 297 (5586): 1556-1559

  Abstract

  The central auditory system translates sound localization cues into a map of space guided, in part, by visual experience. In barn owls, this process takes place in the external nucleus of the inferior colliculus (ICX). However, to date, no trace of visual activity has been observed in this auditory nucleus. Here we show that strong visual responses, which are appropriate to guide auditory plasticity, appear in the ICX when inhibition is blocked in the optic tectum. Thus, visual spatial information is gated into the auditory system by an inhibitory mechanism that operates at a higher level in the brain.

  View details for Web of Science ID 000177697300058

  View details for PubMedID 12202831

• Instructed learning in the auditory localization pathway of the barn owl NATURE Knudsen, E. I. 2002; 417 (6886): 322-328

  Abstract

  A bird sings and you turn to look at it a process so automatic it seems simple. But is it? Our ability to localize the source of a sound relies on complex neural computations that translate auditory localization cues into representations of space. In barn owls, the visual system is important in teaching the auditory system how to translate cues. This example of instructed plasticity is highly quantifiable and demonstrates mechanisms and principles of learning that may be used widely throughout the central nervous system.

  View details for Web of Science ID 000175592100056

  View details for PubMedID 12015612

• The optic tectum controls visually guided adaptive plasticity in the owl's auditory space map NATURE Hyde, P. S., Knudsen, E. I. 2002; 415 (6867): 73-76

  Abstract

  The midbrain contains an auditory map of space that is shaped by visual experience. When barn owls are raised wearing spectacles that horizontally displace the visual field, the auditory space map in the external nucleus of the inferior colliculus (ICX) shifts according to the optical displacement of the prisms. Topographic visual activity in the optic tectum could serve as the template that instructs the auditory space map. We studied the effects of a restricted, unilateral lesion in the portion of the optic tectum that represents frontal space. Here we show that such a lesion eliminates adaptive adjustments specifically in the portion of the auditory map that represents frontal space on the same side of the brain, while the rest of the map continues to adjust adaptively. Thus, activity in the tectum calibrates the auditory space map in a location-specific manner. Because the site of adaptive changes is the ICX, the results also indicate that the tectum provides a topographic instructive signal that controls adaptive auditory plasticity in the ICX.

  View details for Web of Science ID 000173028800042

  View details for PubMedID 11780119

• A topographic instructive signal guides the adjustment of the auditory space map in the optic tectum JOURNAL OF NEUROSCIENCE Hyde, P. S., Knudsen, E. I. 2001; 21 (21): 8586-8593

  Abstract

  Maps of auditory space in the midbrain of the barn owl (Tyto alba) are calibrated by visual experience. When owls are raised wearing prismatic spectacles that displace the visual field in azimuth, the auditory receptive fields of neurons in the optic tectum shift to compensate for the optical displacement of the visual field. This shift results primarily from a shift in the tuning of tectal neurons for interaural time difference. The visually based instructive signal that guides this plasticity could be based on a topographic, point-by-point comparison between auditory and visual space maps or on a foveation-dependent visual assessment of the accuracy of auditory orienting responses. To distinguish between these two possibilities, we subjected owls to optical conditions that differed in the center of gaze and the visual periphery. A topographic signal would cause the portions of the space map representing the central and peripheral regions of visual space to adjust differently, according to the optical conditions that exist in each region. In contrast, a foveation-based signal would cause both portions of the map to adjust similarly, according to the optical conditions that exist at the center of gaze. In six of seven experiments, adaptive changes were as predicted by a topographic instructive signal. Although the results do not rule out the possible contribution of a foveation-based signal, they demonstrate that a topographic instructive signal is, indeed, involved in the calibration of the auditory space map in the barn owl optic tectum.

  View details for Web of Science ID 000171608600037

  View details for PubMedID 11606646

• GABAergic inhibition antagonizes adaptive adjustment of the owl's auditory space map during the initial phase of plasticity JOURNAL OF NEUROSCIENCE Zheng, W. M., Knudsen, E. I. 2001; 21 (12): 4356-4365

  Abstract

  We studied the influence of GABA-mediated inhibition on adaptive adjustment of the owl's auditory space map during the initial phase of plasticity. Plasticity of the auditory space map was induced by subjecting owls to a chronic prismatic displacement of the visual field. In the initial stages of plasticity, inhibition suppressed responses to behaviorally appropriate, newly functional excitatory inputs. As a result, adaptive changes in excitatory input were only partially expressed as postsynaptic spike activity. This masking effect of inhibition on map plasticity did not depend on the activity of NMDA receptors at the synapses that supported the newly learned responses. On the basis of these results, we propose that the pattern of feedforward inhibition is less dynamic than the pattern of feedforward excitation at the site of plasticity. As a result, initially in the adjustment process the preexisting pattern of feedforward GABAergic inhibition opposes changes in the auditory space map and tends to preserve the established response properties of the network. The implications of this novel role of inhibition for the functional plasticity of the brain are discussed.

  View details for Web of Science ID 000169279900027

  View details for PubMedID 11404421

• Adaptive axonal remodeling in the midbrain auditory space map JOURNAL OF NEUROSCIENCE DeBello, W. M., Feldman, D. E., Knudsen, E. I. 2001; 21 (9): 3161-3174

  Abstract

  The auditory space map in the external nucleus of the inferior colliculus (ICX) of barn owls is highly plastic, especially during early life. When juvenile owls are reared with prismatic spectacles (prisms) that displace the visual field laterally, the auditory spatial tuning of neurons in the ICX adjusts adaptively to match the visual displacement. In the present study, we show that this functional plasticity is accompanied by axonal remodeling. The ICX receives auditory input from the central nucleus of the inferior colliculus (ICC) via topographic axonal projections. We used the anterograde tracer biocytin to study experience-dependent changes in the spatial pattern of axons projecting from the ICC to the ICX. The projection fields in normal adults were sparser and more restricted than those in normal juveniles. The projection fields in prism-reared adults were denser and broader than those in normal adults and contained substantially more bouton-laden axons that were appropriately positioned in the ICX to convey adaptive auditory spatial information. Quantitative comparison of results from juvenile and prism-reared owls indicated that prism experience led to topographically appropriate axonal sprouting and synaptogenesis. We conclude that this elaboration of axons represents the formation of an adaptive neuronal circuit. The density of axons and boutons in the normal projection zone was preserved in prism-reared owls. The coexistence of two different circuits encoding alternative maps of space may underlie the ability of prism-reared owls to readapt to normal conditions as adults.

  View details for Web of Science ID 000168182900028

  View details for PubMedID 11312301

• Early auditory experience induces frequency-specific, adaptive plasticity in the forebrain gaze fields of the barn owl JOURNAL OF NEUROPHYSIOLOGY Miller, G. L., Knudsen, E. I. 2001; 85 (5): 2184-2194

  Abstract

  Binaural acoustic cues such as interaural time and level differences (ITDs and ILDs) are used by many species to determine the locations of sound sources. The relationship between cue values and locations in space is frequency dependent and varies from individual to individual. In the current study, we tested the capacity of neurons in the forebrain localization pathway of the barn owl to adjust their tuning for binaural cues in a frequency-dependent manner in response to auditory experience. Auditory experience was altered by raising young owls with a passive acoustic filtering device that caused frequency-dependent changes in ITD and ILD. Extracellular recordings were made in normal and device-reared owls to characterize frequency-specific ITD and ILD tuning in the auditory archistriatum (AAr), an output structure of the forebrain localization pathway. In device-reared owls, individual sites in the AAr exhibited highly abnormal, frequency-dependent variations in ITD tuning, and across the population of sampled sites, there were frequency-dependent shifts in the representation of ITD. These changes were in a direction that compensated for the acoustic effects of the device on ITD and therefore tended to restore a normal representation of auditory space. Although ILD tuning was degraded relative to normal at many sites in the AAr of device-reared owls, the representation of frequency-specific ILDs across the population of sampled sites was shifted in the adaptive direction. These results demonstrate that early auditory experience shapes the representation of binaural cues in the forebrain localization pathway in an adaptive, frequency-dependent manner.

  View details for Web of Science ID 000168675100037

  View details for PubMedID 11353033

• Adaptive adjustment of connectivity in the inferior colliculus revealed by focal pharmacological inactivation JOURNAL OF NEUROPHYSIOLOGY Gold, J. I., Knudsen, E. I. 2001; 85 (4): 1575-1584

  Abstract

  In the midbrain sound localization pathway of the barn owl, a map of auditory space is synthesized in the external nucleus of the inferior colliculus (ICX) and transmitted to the optic tectum. Early auditory experience shapes these maps of auditory space in part by modifying the tuning of the constituent neurons for interaural time difference (ITD), a primary cue for sound-source azimuth. Here we show that these adaptive modifications in ITD tuning correspond to changes in the pattern of connectivity within the inferior colliculus. We raised owls with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. As reported previously, device rearing shifted the representation of ITD in the ICX and tectum but not in the primary source of input to the ICX, the central nucleus of the inferior colliculus (ICC). We applied the local anesthetic lidocaine (QX-314) iontophoretically in the ICC to inactivate small populations of neurons that represented particular values of frequency and ITD. We measured the effect of this inactivation in the optic tecta of a normal owl and owls raised with the device. In the normal owl, inactivation at a critical site in the ICC eliminated responses in the tectum to the frequency-specific ITD value represented at the site of inactivation in the ICC. The location of this site was consistent with the known pattern of ICC-ICX-tectum connectivity. In the device-reared owls, adaptive changes in the representation of ITD in the tectum corresponded to dramatic and predictable changes in the locations of the critical sites of inactivation in the ICC. Given that the abnormal representation of ITD in the tectum depended on frequency and was likely conveyed directly from the ICX, these results suggest that experience causes large-scale, frequency-specific adjustments in the pattern of connectivity between the ICC and the ICX.

  View details for Web of Science ID 000167866700023

  View details for PubMedID 11287481

• Traces of learning in the auditory localization pathway National Academy of Sciences Colloquium on Auditory Neuroscience - Development, Transduction, and Integration Knudsen, E. I., Zheng, W. M., DeBello, W. M. NATL ACAD SCIENCES. 2000: 11815–20

  Abstract

  One of the fascinating properties of the central nervous system is its ability to learn: the ability to alter its functional properties adaptively as a consequence of the interactions of an animal with the environment. The auditory localization pathway provides an opportunity to observe such adaptive changes and to study the cellular mechanisms that underlie them. The midbrain localization pathway creates a multimodal map of space that represents the nervous system's associations of auditory cues with locations in visual space. Various manipulations of auditory or visual experience, especially during early life, that change the relationship between auditory cues and locations in space lead to adaptive changes in auditory localization behavior and to corresponding changes in the functional and anatomical properties of this pathway. Traces of this early learning persist into adulthood, enabling adults to reacquire patterns of connectivity that were learned initially during the juvenile period.

  View details for Web of Science ID 000090071000024

  View details for PubMedID 11050214

• Topographic projection from the optic tectum to the auditory space map in the inferior colliculus of the barn owl JOURNAL OF COMPARATIVE NEUROLOGY Hyde, P. S., Knudsen, E. I. 2000; 421 (2): 146-160

  Abstract

  In the barn owl (Tyto alba), the external nucleus of the inferior colliculus (ICX) contains a map of auditory space that is calibrated by visual experience. The source of the visually based instructive signal to the ICX is unknown. Injections of biotinylated dextran amine and Fluoro-Gold in the ICX retrogradely labelled neurons in layers 8-15 of the ipsilateral optic tectum (OT) that could carry this instructive signal. This projection was point-to-point and in register with the feed-forward, auditory projection from the ICX to the OT. Most labelled neurons were in layers 10-11, and most were bipolar. Tripolar, multipolar, and unipolar neurons were also observed. Multipolar neurons had dendrites that were oriented parallel to the tectal laminae. In contrast, most labelled bipolar and tripolar neurons had dendrites oriented perpendicular to the tectal laminae, extending superficially into the retino-recipient laminae and deep into the auditory recipient laminae. Therefore, these neurons were positioned to receive both visual and auditory information from particular locations in space. Biocytin injected into the superficial layers of the OT labelled bouton-laden axons in the ICX. These axons were generally finer than, but had similar bouton densities as, feed-forward auditory fibers in the ICX, labelled by injections of biocytin into the central nucleus of the inferior colliculus (ICC). These data demonstrate a point-to-point projection from the OT to the ICX that could provide a spatial template for calibrating the auditory space map in the ICX.

  View details for Web of Science ID 000086786200002

  View details for PubMedID 10813778

• A site of auditory experience-dependent plasticity in the neural representation of auditory space in the barn owl's inferior colliculus JOURNAL OF NEUROSCIENCE Gold, J. I., Knudsen, E. I. 2000; 20 (9): 3469-3486

  Abstract

  The barn owl's optic tectum contains a map of auditory space that is based, in part, on a map of interaural time difference (ITD). Previous studies have shown that this ITD map is shaped by auditory experience. In this study, we investigated whether the plasticity responsible for experience-induced changes in ITD tuning in the tectum occurs within the tectum itself or at an earlier stage in the auditory pathway. We altered auditory experience in young owls by implanting an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. We analyzed the representation of ITD in normal and device-reared owls in two nuclei in the ascending pathway: the external nucleus of the inferior colliculus (ICX), the primary source of ascending auditory input to the tectum, and the lateral shell of the central nucleus of the inferior colliculus (ICCls), the primary source of input to the ICX. In the ICX, device rearing caused adaptive, frequency-dependent changes in ITD tuning, as well as changes in frequency tuning. These changes in tuning were similar to changes that occurred in the optic tectum in the same owls. In contrast, in the ICCls, tuning for ITD and frequency was unaffected by device rearing. The data indicate that plasticity at the level of the ICX is largely responsible for the adaptive adjustments in ITD tuning and frequency tuning that are observed in the optic tecta of owls raised with abnormal auditory experience.

  View details for Web of Science ID 000086783000044

  View details for PubMedID 10777810

• Abnormal auditory experience induces frequency-specific adjustments in unit tuning for binaural localization cues in the optic tectum of juvenile owls JOURNAL OF NEUROSCIENCE Gold, J. I., Knudsen, E. I. 2000; 20 (2): 862-877

  Abstract

  Early auditory experience shapes the auditory spatial tuning of neurons in the barn owl's optic tectum in a frequency-dependent manner. We examined the basis for this adaptive plasticity in terms of changes in tuning for frequency-specific interaural time differences (ITDs) and level differences (ILDs), the dominant sound localization cues. We characterized broadband and narrowband ITD and ILD tuning in normal owls and in owls raised with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. In normal owls, units were tuned to frequency-specific ITD and ILD values that matched those produced by sound sources located in their visual receptive fields. In contrast, in device-reared owls, ITD tuning at most sites was shifted from normal by approximately 55 microsec toward open-ear leading for 4 kHz stimuli and 15 microsec toward the opposite-ear leading for 8 kHz stimuli, reflecting the acoustic effects of the device. ILD tuning was shifted in the adaptive direction by approximately 3 dB for 4 kHz stimuli and 8 dB for 8 kHz stimuli, but these shifts were substantially smaller than expected based on the acoustic effects of the device. Most sites also exhibited conspicuously abnormal frequency-response functions, including a strong dependence on stimulus ITD and a reduction of normally robust responses to 6 kHz stimuli. The results demonstrate that the response properties of high-order auditory neurons in the optic tectum are adjusted during development to reflect the influence of frequency-specific features of the binaural localization cues experienced by the individual.

  View details for Web of Science ID 000084929600040

  View details for PubMedID 10632616

• Hearing impairment induces frequency-specific adjustments in auditory spatial tuning in the optic tectum of young owls JOURNAL OF NEUROPHYSIOLOGY Gold, J. I., Knudsen, E. I. 1999; 82 (5): 2197-2209

  Abstract

  Bimodal, auditory-visual neurons in the optic tectum of the barn owl are sharply tuned for sound source location. The auditory receptive fields (RFs) of these neurons are restricted in space primarily as a consequence of their tuning for interaural time differences and interaural level differences across broad ranges of frequencies. In this study, we examined the extent to which frequency-specific features of early auditory experience shape the auditory spatial tuning of these neurons. We manipulated auditory experience by implanting in one ear canal an acoustic filtering device that altered the timing and level of sound reaching the eardrum in a frequency-dependent fashion. We assessed the auditory spatial tuning at individual tectal sites in normal owls and in owls raised with the filtering device. At each site, we measured a family of auditory RFs using broadband sound and narrowband sounds with different center frequencies both with and without the device in place. In normal owls, the narrowband RFs for a given site all included a common region of space that corresponded with the broadband RF and aligned with the site's visual RF. Acute insertion of the filtering device in normal owls shifted the locations of the narrowband RFs away from the visual RF, the magnitude and direction of the shifts depending on the frequency of the stimulus. In contrast, in owls that were raised wearing the device, narrowband and broadband RFs were aligned with visual RFs so long as the device was in the ear but not after it was removed, indicating that auditory spatial tuning had been adaptively altered by experience with the device. The frequency tuning of tectal neurons in device-reared owls was also altered from normal. The results demonstrate that experience during development adaptively modifies the representation of auditory space in the barn owl's optic tectum in a frequency-dependent manner.

  View details for Web of Science ID 000083875700019

  View details for PubMedID 10561399

• Mechanisms of experience-dependent plasticity in the auditory localization pathway of the barn owl JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY Knudsen, E. I. 1999; 185 (4): 305-321

  Abstract

  Sound localization is a computational process that requires the central nervous system to measure various auditory cues and then associate particular cue values with appropriate locations in space. Behavioral experiments show that barn owls learn to associate values of cues with locations in space based on experience. The capacity for experience-driven changes in sound localization behavior is particularly great during a sensitive period that lasts until the approach of adulthood. Neurophysiological techniques have been used to determine underlying sites of plasticity in the auditory space-processing pathway. The external nucleus of the inferior colliculus (ICX), where a map of auditory space is synthesized, is a major site of plasticity. Experience during the sensitive period can cause large-scale, adaptive changes in the tuning of ICX neurons for sound localization cues. Large-scale physiological changes are accompanied by anatomical remodeling of afferent axons to the ICX. Changes in the tuning of ICX neurons for cue values involve two stages: (1) the instructed acquisition of neuronal responses to novel cue values and (2) the elimination of responses to inappropriate cue values. Newly acquired neuronal responses depend differentially on NMDA receptor currents for their expression. A model is presented that can account for this adaptive plasticity in terms of plausible cellular mechanisms.

  View details for Web of Science ID 000083625700004

  View details for PubMedID 10555267

• Functional selection of adaptive auditory space map by GABA(A)-mediated inhibition SCIENCE Zheng, W. M., Knudsen, E. I. 1999; 284 (5416): 962-965

  Abstract

  The external nucleus of the inferior colliculus in the barn owl contains an auditory map of space that is based on the tuning of neurons for interaural differences in the timing of sound. In juvenile owls, this region of the brain can acquire alternative maps of interaural time difference as a result of abnormal experience. It has been found that, in an external nucleus that is expressing a learned, abnormal map, the circuitry underlying the normal map still exists but is functionally inactivated by inhibition mediated by gamma-aminobutyric acid type A (GABAA) receptors. This inactivation results from disproportionately strong inhibition of specific input channels to the network. Thus, experience-driven changes in patterns of inhibition, as well as adjustments in patterns of excitation, can contribute critically to adaptive plasticity in the central nervous system.

  View details for Web of Science ID 000080198800045

  View details for PubMedID 10320376

• Early visual experience shapes the representation of auditory space in the forebrain gaze fields of the barn owl JOURNAL OF NEUROSCIENCE Miller, G. L., Knudsen, E. I. 1999; 19 (6): 2326-2336

  Abstract

  Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain. Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls. This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli.

  View details for Web of Science ID 000078961400040

  View details for PubMedID 10066282

• Maps versus clusters: different representations of auditory space in the midbrain and forebrain TRENDS IN NEUROSCIENCES Cohen, Y. E., Knudsen, E. I. 1999; 22 (3): 128-135

  Abstract

  The auditory system determines the location of stimuli based on the evaluation of specific cues. The analysis begins in the tonotopic pathway, where these cues are processed in parallel, frequency-specific channels. This frequency-specific information is processed further in the midbrain and in the forebrain by specialized, space-processing pathways that integrate information across frequency channels, creating high-order neurons tuned to specific locations in space. Remarkably, the results of this integrative step are represented very differently in the midbrain and forebrain: in the midbrain, space is represented in maps, whereas, in the forebrain, space is represented in clusters of similarly tuned neurons. We propose that these different representations reflect the different roles that these two brain areas have in guiding behavior.

  View details for Web of Science ID 000079418300008

  View details for PubMedID 10199638

• Experience-dependent plasticity and the maturation of glutamatergic synapses NEURON Feldman, D. E., Knudsen, E. I. 1998; 20 (6): 1067-1071

  View details for Web of Science ID 000074627300004

  View details for PubMedID 9655495

• Sensitive periods for visual calibration of the auditory space map in the barn owl optic tectum JOURNAL OF NEUROSCIENCE Brainard, M. S., Knudsen, E. I. 1998; 18 (10): 3929-3942

  Abstract

  Previous studies have identified sensitive periods for the developing barn owl during which visual experience has a powerful influence on the calibration of sound localization behavior. Here we investigated neural correlates of these sensitive periods by assessing developmental changes in the capacity of visual experience to alter the map of auditory space in the optic tectum of the barn owl. We used two manipulations. (1) We equipped owls with prismatic spectacles that optically displaced the visual field by 23 degrees to the left or right, and (2) we restored normal vision to prism-reared owls that had been raised wearing prisms. In agreement with previous behavioral experiments, we found that the capacity of abnormal visual experience to shift the tectal auditory space map was restricted to an early sensitive period. However, this period extended until later in life (approximately 200 d) than described previously in behavioral studies (approximately 70 d). Furthermore, unlike the previous behavioral studies that found that the capacity to recover normal sound localization after restoration of normal vision was lost at approximately 200 d of age, we found that the capacity to recover a normal auditory space map was never lost. Finally, we were able to reconcile the behaviorally and neurophysiologically defined sensitive periods by taking into account differences in the richness of the environment in the two sets of experiments. We repeated the behavioral experiments and found that when owls were housed in a rich environment, the capacity to adjust sound localization away from normal extended to later in life, whereas the capacity to recover to normal was never lost. Conversely, when owls were housed in an impoverished environment, the capacity to recover a normal auditory space map was restricted to a period ending at approximately 200 d of age. The results demonstrate that the timing and even the existence of sensitive periods for plasticity of a neural circuit and associated behavior can depend on multiple factors, including (1) the nature of the adjustment demanded of the system and (2) the richness of the sensory and social environment in which the plasticity is studied.

  View details for Web of Science ID 000073484300041

  View details for PubMedID 9570820

• Pharmacological specialization of learned auditory responses in the inferior colliculus of the barn owl JOURNAL OF NEUROSCIENCE Feldman, D. E., Knudsen, E. I. 1998; 18 (8): 3073-3087

  Abstract

  Neural tuning for interaural time difference (ITD) in the optic tectum of the owl is calibrated by experience-dependent plasticity occurring in the external nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a sustained lateral displacement of the visual field by wearing prismatic spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX neurons acquire novel auditory responses, termed "learned responses," to ITD values outside their normal, pre-existing tuning range. In this study, we compared the glutamatergic pharmacology of learned responses with that of normal responses expressed by the same ICX neurons. Measurements were made in the ICX using iontophoretic application of glutamate receptor antagonists. We found that in early stages of ITD tuning adjustment, soon after learned responses had been induced by experience-dependent processes, the NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of learned responses of many ICX neurons compared with that of normal responses of the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally. After long periods of prism experience, preferential blockade of learned responses by AP-5 was no longer observed. These results indicate that NMDA receptors play a preferential role in the expression of learned responses soon after these responses have been induced by experience-dependent processes, whereas later in development or with additional prism experience (we cannot distinguish which), the differential NMDA receptor-mediated component of these responses disappears. This pharmacological progression resembles the changes that occur during maturation of glutamatergic synaptic currents during early development.

  View details for Web of Science ID 000072933300028

  View details for PubMedID 9526024

• Capacity for plasticity in the adult owl auditory system expanded by juvenile experience SCIENCE Knudsen, E. I. 1998; 279 (5356): 1531-1533

  Abstract

  In the process of creating a multimodal map of space, auditory-visual neurons in the optic tectum establish associations between particular values of auditory spatial cues and locations in the visual field. In the barn owl, tectal neurons reveal these associations in the match between their tuning for interaural time differences (ITDs) and the locations of their visual receptive fields (VRFs). In young owls ITD-VRF associations can be adjusted by experience over a wide range, but the range of adjustment normally becomes quite restricted in adults. This normal range of adjustment in adults was greatly expanded in owls that had previously learned abnormal ITD-VRF associations as juveniles. Thus, the act of learning abnormal associations early in life leaves an enduring trace in this pathway that enables unusual functional connections to be reestablished, as needed, in adulthood, even when the associations represented by these connections have not been used for an extended period of time.

  View details for Web of Science ID 000072372900064

  View details for PubMedID 9488651

• Forebrain pathway for auditory space processing in the barn owl JOURNAL OF NEUROPHYSIOLOGY Cohen, Y. E., Miller, G. L., Knudsen, E. I. 1998; 79 (2): 891-902

  Abstract

  The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway.

  View details for Web of Science ID 000072115600034

  View details for PubMedID 9463450

• Representation of binaural spatial cues in Field L of the barn owl forebrain JOURNAL OF NEUROPHYSIOLOGY Cohen, Y. E., Knudsen, E. I. 1998; 79 (2): 879-890

  Abstract

  This study examined the representation of spatial information in the barn owl Field L, the first telencephalic processing stage of the classical auditory pathway. Field L units were recorded extracellularly, and their responses to dichotically presented interaural time differences (ITD) and interaural level differences (ILD) were tested. We observed a variety of tuning profiles in Field L. Some sites were not sensitive to ITD or ILD. Other sites, especially those in the high-frequency region, were highly selective for values of ITD and ILD. These sites had multipeaked (commonly called "phase ambiguous") ITD tuning profiles and were tuned for a single value of ILD. The tuning properties of these sites are similar to those seen in the lateral shell of the central nucleus of the inferior colliculus. Although the tuning properties of Field L sites were similar to those observed in the inferior colliculus, the functional organization of this spatial information was fundamentally different. Whereas in the inferior colliculus spatial information is organized into global topographics maps, in Field L spatial information is organized into local clusters, with sites having similar binaural tuning properties grouped together. The representation of binaural cues in Field L suggests that it is involved in auditory space processing but at a lower level of information processing than the auditory archistriatum, a forebrain area that is specialized for processing spatial information, and that the levels of information processing in the forebrain space processing pathway are remarkably similar to those in the well-known midbrain space processing pathway.

  View details for Web of Science ID 000072115600033

  View details for PubMedID 9463449

• An anatomical basis for visual calibration of the auditory space map in the barn owl's midbrain JOURNAL OF NEUROSCIENCE Feldman, D. E., Knudsen, E. I. 1997; 17 (17): 6820-6837

  Abstract

  The map of auditory space in the external nucleus of the inferior colliculus (ICX) of the barn owl is calibrated by visual experience during development. ICX neurons are tuned for interaural time difference (ITD), the owl's primary cue for sound source azimuth, and are arranged into a map of ITD. When vision is altered by rearing owls with prismatic spectacles that shift the visual field in azimuth, ITD tuning in the ICX shifts adaptively. In contrast, ITD tuning remains unchanged in the lateral shell of the central nucleus of the inferior colliculus (ICCls), which provides the principal auditory input to the ICX, suggesting that the projection from the ICCls to the ICX is altered by prism-rearing. In this study, the topography of the ICCls-ICX projection was assessed in normal and prism-reared owls by retrograde labeling using biotinylated dextran amine. In juvenile owls at the age before prism attachment, and in normal adults, labeling patterns were consistent with a topographic projection, with each ICX site receiving input from a restricted region of the ICCls with similar ITD tuning. In prism-reared owls, labeling patterns were systematically altered: each ICX site received additional, abnormal input from a region of the ICCls where ITD tuning matched the shifted ITD tuning of the ICX neurons. These results indicate that anatomical reorganization of the ICCls-ICX projection contributes to the visual calibration of the ICX auditory space map.

  View details for Web of Science ID A1997XT28300032

  View details for PubMedID 9254692

• Representation of frequency in the primary auditory field of the barn owl forebrain JOURNAL OF NEUROPHYSIOLOGY Cohen, Y. E., Knudsen, E. I. 1996; 76 (6): 3682-3692

  Abstract

  1. The primary auditory field (PAF) constitutes the first telencephalic stage of auditory information processing in the classical auditory pathway. In this study we investigated the frequency representation in the PAF of the barn owl, a species with a broad frequency range of hearing and a highly advanced auditory system. 2. Single- and multiunit sites were recorded extracellularly in ketamine-anesthetized owls. The frequency response properties of PAF sites were assessed with the use of digitally synthesized dichotic stimuli. PAF sites (n = 442) either were unresponsive to tonal stimulation (but responsive to noise stimuli), were tuned for frequency, or had multipeaked frequency response profiles. Tuned sites responded best to frequencies between 0.2 and 8.8 kHz, a range that encompasses nearly the entire hearing range of the barn owl. Most sites responding best to frequencies < 4 kHz had relatively broad frequency tuning, whereas sites responding best to higher frequencies had either broad or narrow frequency tuning. Sites with multipeaked frequency response profiles typically had two response peaks. The first peak was usually between 1 and 3 kHz and the second was usually between 5 and 8 kHz; there was no systematic relationship between the two peak frequencies. 3. In dorsoventral electrode penetrations that contained sites with tuned and/or multipeaked response profiles, a "common frequency" was identified that elicited a maximal response from all of the sites in the penetration. 4. The PAF contains a single tonotopic field. Units tuned to low frequencies are located caudomedially, whereas units tuned to high frequencies are located rostrolaterally. Compared with the frequency representation along the basilar papilla and in other auditory structures, the PAF overrepresents low frequencies (< 4 kHz) that are important for barn owl vocalizations. Conversely, high frequencies (> or = 4 kHz), which are necessary for precise sound localization, are underrepresented relative to these more peripheral auditory structures. 5. There was considerable interindividual variability both in the relative magnification of different frequency ranges and in the orientation of the tonotopic map in the brain. 6. These results suggest that the barn owl PAF, like the mammalian primary auditory cortex, is a general processor of auditory information that is involved in the analysis of both the meaning (such as species-specific vocalizations) and the location of auditory stimuli. In addition, the high degree of interindividual variability in the representation of frequency information suggests that the barn owl PAF, like the mammalian auditory cortex, is subject to modification by sensory experience.

  View details for Web of Science ID A1996WA80300008

  View details for PubMedID 8985866

• Disruption of auditory spatial working memory by inactivation of the forebrain archistriatum in barn owls NATURE Knudsen, E. I., KNUDSEN, P. F. 1996; 383 (6599): 428-431

  Abstract

  Barn owls not only localize auditory stimuli with great accuracy, they also remember the locations of auditory stimuli and can use this remembered spatial information to guide their flight and strike. Although the mechanisms of sound localization have been studied extensively, the neurobiological basis of auditory spatial memory has not. Here we show that the ability of barn owls to orient their gaze towards and fly to the remembered location of auditory targets is lost during pharmacological inactivation of a small region in the forebrain, the anterior archistriatum. In contrast, archistriatal inactivation has no effect on stimulus-guided responses to auditory targets. The memory-dependent deficit is evident only for acoustic events that occur in the hemifield contralateral to the side that is inactivated. The data demonstrate that in the avian archistriatum, as in the mammalian frontal cortex, there exists a region that is essential for the expression of spatial working memory and that, in the barn owl, this region encodes auditory spatial memory.

  View details for Web of Science ID A1996VL46300059

  View details for PubMedID 8837773

• Contribution of the forebrain archistriatal gaze fields to auditory orienting behavior in the barn owl EXPERIMENTAL BRAIN RESEARCH Knudsen, E. I., KNUDSEN, P. F. 1996; 108 (1): 23-32

  Abstract

  A region in the barn owl forebrain, referred to as the archistriatal gaze fields (AGF), is shown to be involved in auditory orienting behavior. In a previous study, electrical microstimulation of the AGF was shown to produce saccadic movements of the eyes and head, and anatomical data revealed that neurons in the AGF region of the archistriatum project directly to brainstem tegmental nuclei that mediate gaze changes. In this study, we investigated the effects of AGF inactivation on the auditory orienting responses of trained barn owls. The AGF and/or the optic tectum (OT) were inactivated pharmacologically using the GABAA agonist muscimol. Inactivation of the AGF alone had no effect on the probability or accuracy of orienting responses to contralateral acoustic stimuli. Inactivation of the OT alone decreased the probability of responses to contralateral stimuli, but the animals were still capable of orienting accurately toward stimuli on about 60% of the trials. Inactivation of both the AGF and the OT drastically decreased the probability of responses to 16-21% and, on the few trials that the animals did respond, there was no relationship between the final direction of gaze and the location of the stimulus. Thus, with the AGF and OT both inactivated, the animals were no longer capable of orienting accurately toward acoustic stimuli located on the contralateral side. These data confirm that the AGF is involved in gaze control and that the AGF and the OT have parallel access to gaze control circuitry in the brainstem tegmentum. In these respects, the AGF in barn owls is functionally equivalent to the frontal eye fields in primates.

  View details for Web of Science ID A1996TZ42000003

  View details for PubMedID 8721152

• Newly learned auditory responses mediated by NMDA receptors in the owl inferior colliculus SCIENCE Feldman, D. E., Brainard, M. S., Knudsen, E. I. 1996; 271 (5248): 525-528

  Abstract

  Alignment of auditory and visual receptive fields in the optic tectum of the barn owl (Tyto alba) is maintained through experience-dependent modification of auditory responses in the external nucleus of the inferior colliculus (ICX), which provides auditory input to the tectum. Newly learned tectal auditory responses, induced by altered visual experience, were found to be pharmacologically distinct from normal responses expressed at the same tectal sites. N-methyl-D-aspartate (NMDA) receptor antagonists administered systemically or applied locally in the ICX reduced learned responses more than normal responses. This differential blockade was not observed with non-NMDA or broad-spectrum antagonists. Thus, NMDA receptors preferentially mediate the expression of novel neuronal responses induced by experience during development.

  View details for Web of Science ID A1996TR32200048

  View details for PubMedID 8560271

• BINAURAL TUNING OF AUDITORY UNITS IN THE FOREBRAIN ARCHISTRIATAL GAZE FIELDS OF THE BARN OWL - LOCAL-ORGANIZATION BUT NO SPACE MAP JOURNAL OF NEUROSCIENCE Cohen, Y. E., Knudsen, E. I. 1995; 15 (7): 5152-5168

  Abstract

  We identified a region in the archistriatum of the barn owl forebrain that contains neurons sensitive to auditory stimuli. Nearly all of these neurons are tuned for binaural localization cues. The archistriatum is known to be the primary source of motor-related output from the avian forebrain and, in barn owls, contributes to the control of gaze, much like the frontal eye fields in monkeys. The auditory region is located in the medial portion of the archistriatum, at the level of the anterior commissure, and is within the region of the archistriatum from which head saccades can be elicited by electrical microstimulation (see preceding companion article, Knudsen et al., 1995). Free-field measurements revealed that auditory sites have large, spatial receptive fields. However, within these large receptive fields, responses are tuned sharply for sound source location. Dichotic measurements showed that auditory sites are tuned broadly for frequency and that the majority are tuned to particular values of interaural time differences and interaural level differences, the principal cues used by barn owls for sound localization. The tuning of sites to these binaural cues is essentially independent of sound level. The auditory properties of units in the medial archistriatum are similar to those of units in the optic tectum, a structure that also contributes to gaze control. Unlike the optic tectum, however, the auditory region of the archistriatum does not contain a single, continuous auditory map of space. Instead, it is organized into dorsoventral clusters of sites with similar binaural (spatial) tuning. The different representations of auditory space in closely related structures in the forebrain (archistriatum) and midbrain (optic tectum) probably reflect the fact that the forebrain contributes to a wide variety of sensorimotor tasks more complicated than gaze control.

  View details for Web of Science ID A1995RJ66600007

  View details for PubMedID 7623142

• CHARACTERIZATION OF A FOREBRAIN GAZE FIELD IN THE ARCHISTRIATUM OF THE BARN OWL - MICROSTIMULATION AND ANATOMICAL CONNECTIONS JOURNAL OF NEUROSCIENCE Knudsen, E. I., Cohen, Y. E., MASINO, T. 1995; 15 (7): 5139-5151

  Abstract

  We present evidence that the archistriatum in the forebrain of the barn owl participates in gaze control, that it can mediate gaze changes independently of the optic tectum (OT), and that it projects in parallel to both the OT and to saccade-generating circuitry in the brainstem tegmentum. These properties are similar to those of the frontal eye fields (FEF) in the prefrontal cortex of primates. The forebrain was surveyed for sites where electrical microstimulation would induce head saccades. Head (and eye) saccades were elicited from the anterior 70% of the archistriatum, a region that we refer to as the archistriatal gaze fields (AGF). At single stimulation sites in the AGF, saccade amplitude tended to vary as a function of stimulation parameters (current strength, pulse frequency, and train duration) and starting head position. In contrast, saccade direction was largely independent of these parameters. Saccade direction did vary over a wide range of primarily contraversive directions with the site of stimulation in the AGF. Using anatomical pathway tracing techniques, we found that the archistriatum projects strongly and in parallel to the deep layers of the OT and to nuclei in the midline brainstem tegmentum. Previous work has shown that electrical microstimulation of either of these brainstem regions evokes saccadic movements of the head and/or eyes (du Lac and Knudsen, 1990; Masino and Knudsen, 1992b). Inactivation of the OT with lidocaine reduced the size but did not eliminate (or change the direction of) the saccades evoked by AGF stimulation. The direct anatomical pathway from the archistriatum to the midline tegmental nuclei can account for saccades that persist following OT inactivation. The similarities between the AGF in barn owls and the FEF in primates suggest that the same general plan of anatomical and functional organization supports the contribution of the forebrain to gaze control in a wide variety of species.

  View details for Web of Science ID A1995RJ66600006

  View details for PubMedID 7623141

• DYNAMICS OF VISUALLY GUIDED AUDITORY PLASTICITY IN THE OPTIC TECTUM OF THE BARN OWL JOURNAL OF NEUROPHYSIOLOGY Brainard, M. S., Knudsen, E. I. 1995; 73 (2): 595-614

  Abstract

  1. In the optic tectum of normal barn owls, bimodal (auditory-visual) neurons are tuned to the values of interaural time difference (ITD) that are produced by sounds at the locations of their visual receptive fields (VRFs). The auditory tuning of tectal neurons is actively guided by visual experience during development: in the tectum of adult owls reared with an optically displaced visual field, neurons are tuned to abnormal values of ITD that are close to the values produced by sounds at the locations of their optically displaced VRFs. In this study we investigated the dynamics of this experience-dependent plasticity. 2. Owls were raised from shortly after eye-opening (14-22 days of age) with prismatic spectacles that displaced the visual field to the right or left. Starting at approximately 60 days of age, multiunit recordings were made to assess the tuning of tectal neurons to ITD presented via earphones. In the earliest recording sessions (ages 60-80 days), ITD tuning was often close to normal, even though the majority of the owls' previous experience was with an altered correspondence between ITD values and VRF locations. Subsequently, over a period of weeks, responses to the normal range of ITDs were gradually eliminated while responses to values of ITD corresponding with the optically displaced VRF were acquired. 3. At intermediate stages in this process, the ITD tuning at many sites became abnormally broad, so that responses were simultaneously present to both normal values of ITD and to values corresponding with the optically displaced VRF. At this stage the latencies and durations of newly acquired responses systematically exceeded the latencies and durations of the responses to normal values of ITD. 4. Dynamic changes in ITD tuning similar to those recorded in the optic tectum also occurred in the external nucleus of the inferior colliculus (ICX), which provides the major source of ascending auditory input to the tectum. 5. These results suggest the hypothesis that the neural selectivity for ITD in the barn owl's tectum is first established by vision-independent mechanisms and only subsequently calibrated by visual experience. This calibration involves both the elimination of responses to normal values of ITD and the visually guided acquisition of responses to novel values and can be accounted for by plasticity at the level of the ICX.

  View details for Web of Science ID A1995QU21500015

  View details for PubMedID 7760121

• CREATING A UNIFIED REPRESENTATION OF VISUAL AND AUDITORY SPACE IN THE BRAIN ANNUAL REVIEW OF NEUROSCIENCE Knudsen, E. I., Brainard, M. S. 1995; 18: 19-43

  View details for Web of Science ID A1995QN29300002

  View details for PubMedID 7605060

• SITE OF AUDITORY PLASTICITY IN THE BRAIN-STEM (VLVP) OF THE OWL REVEALED BY EARLY MONAURAL OCCLUSION JOURNAL OF NEUROPHYSIOLOGY Mogdans, J., Knudsen, E. I. 1994; 72 (6): 2875-2891

  Abstract

  1. The optic tectum of the barn owl contains a physiological map of interaural level difference (ILD) that underlies, in part, its map of auditory space. Monaural occlusion shifts the range of ILDs experienced by an animal and alters the correspondence of ILDs with source locations. Chronic monaural occlusion during development induces an adaptive shift in the tectal ILD map that compensates for the effects of the earplug. The data presented in this study indicate that one site of plasticity underlying this adaptive adjustment is in the posterior division of the ventral nucleus of the lateral lemniscus (VLVp), the first site of ILD comparison in the auditory pathway. 2. Single and multiple unit sites were recorded in the optic tecta and VLVps of ketamine-anesthetized owls. The owls were raised from 4 wk of age with one ear occluded with an earplug. Auditory testing, using digitally synthesized dichotic stimuli, was carried out 8-16 wk later with the earplug removed. The adaptive adjustment in ILD coding in each bird was quantified as the shift from normal ILD tuning measured in the optic tectum. Evidence of adaptive adjustment in the VLVp was based on statistical differences between the VLVp's ipsilateral and contralateral to the occluded ear in the sensitivity of units to excitatory-ear and inhibitory-ear stimulation. 3. The balance of excitatory to inhibitory influences on VLVp units was shifted in the adaptive direction in six out of eight owls. In three of these owls, adaptive differences in inhibition, but not in excitation, were found. For this group of owls, the patterns of response properties across the two VLVps can only be accounted for by plasticity in the VLVp. For the other three owls, the possibility that the difference between the two VLVps resulted from damage to one of the VLVps could not be eliminated, and for one of these, plasticity at a more peripheral site (in the cochlea or cochlear nucleus) could also explain the data. In the remaining two owls, there was no evidence of adaptive adjustment in the VLVp despite large adaptive adjustments in the optic tectum. 4. The adjustment of ILD coding in the VLVp was always substantially smaller than expected based on the adjustment of ILD tuning in the optic tectum measured in the same animals. This indicates the involvement of at least one additional site of adaptive plasticity in the auditory pathway above the level of the VLVp.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1994PX46400029

  View details for PubMedID 7897496

• NMDA AND NON-NMDA GLUTAMATE RECEPTORS IN AUDITORY TRANSMISSION IN THE BARN OWL INFERIOR COLLICULUS JOURNAL OF NEUROSCIENCE Feldman, D. E., Knudsen, E. I. 1994; 14 (10): 5939-5958

  Abstract

  The pharmacology of auditory responses in the inferior colliculus (IC) of the barn owl was investigated by iontophoresis of excitatory amino acid receptor antagonists into two different functional subdivisions of the IC, the external nucleus (ICx) and the lateral shell of the central nucleus (lateral shell), both of which carry out important computations in the processing of auditory spatial information. Combined application of the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP5) and the non-NMDA receptor antagonist 6-cyano-5-nitroquinoxaline-2,3-dione (CNQX) significantly reduced auditory-evoked spikes at all sites in these two subdivisions, and completely eliminated responses at many locations. This suggests that excitatory amino acid receptors mediate the bulk, if not all, of auditory responses in the ICx and lateral shell. NMDA and non-NMDA receptors contributed differently to auditory responses in the two subdivisions. In the ICx, AP5 significantly reduced the number of auditory-evoked spikes at every site tested. On average, AP5 eliminated 55% of auditory-evoked spikes at multiunit sites and 64% at single-unit sites in this structure. In contrast, in the lateral shell, AP5 significantly reduced responses at less than half the sites tested, and, on average, AP5 eliminated only 19% of spikes at multiunit sites and 25% at single-unit sites. When the magnitude of response blockade produced by AP5 at individual multiunit sites was normalized to adjust for site-to-site differences in the efficacy of iontophoresed AP5 and CNQX, AP5 blockade was still significantly greater in the ICx than the lateral shell. CNQX application strongly reduced responses in both subdivisions. These data suggest that NMDA receptor currents make a major contribution to auditory responses in the ICx, while they make only a small contribution to auditory responses in the lateral shell. Non-NMDA receptor currents, on the other hand, contribute to auditory responses in both subdivisions, and mediate the bulk of auditory transmission in the lateral shell. The time course of the NMDA receptor contribution to ICx auditory responses and the dependence of this contribution on stimulus level were both examined in detail. AP5 preferentially blocked spikes late in ICx auditory responses, while CNQX blocked spikes equally throughout the responses. This pattern is consistent with a simple model in which slow NMDA receptor currents and faster non-NMDA receptor currents are both activated by auditory inputs to ICx neurons.

  View details for Web of Science ID A1994PL02800018

  View details for PubMedID 7931555

• SUPERVISED LEARNING IN THE BRAIN JOURNAL OF NEUROSCIENCE Knudsen, E. I. 1994; 14 (7): 3985-3997

  View details for Web of Science ID A1994NZ62000001

  View details for PubMedID 8027757

• AUDITORY TUNING FOR SPATIAL CUES IN THE BARN OWL BASAL GANGLIA JOURNAL OF NEUROPHYSIOLOGY Cohen, Y. E., Knudsen, E. I. 1994; 72 (1): 285-298

  Abstract

  1. The basal ganglia are known to contribute to spatially guided behavior. In this study, we investigated the auditory response properties of neurons in the barn owl paleostriatum augmentum (PA), the homologue of the mammalian striatum. The data suggest that the barn owl PA is specialized to process spatial cues and, like the mammalian striatum, is involved in spatial behavior. 2. Single- and multiunit sites were recorded extracellularly in ketamine-anesthetized owls. Spatial receptive fields were measured with a free-field sound source, and tuning for frequency and interaural differences in timing (ITD) and level (ILD) was assessed using digitally synthesized dichotic stimuli. 3. Spatial receptive fields measured at nine multiunit sites were tuned to restricted regions of space: tuning widths at half-maximum response averaged 22 +/- 9.6 degrees (mean +/- SD) in azimuth and 54 +/- 22 degrees in elevation. 4. PA sites responded strongly to broadband sounds. When frequency tuning could be measured (n = 145/201 sites), tuning was broad, averaging 2.7 kHz at half-maximum response, and tended to be centered near the high end of the owl's audible range. The mean best frequency was 6.2 kHz. 5. All PA sites (n = 201) were selective for both ITD and ILD. ITD tuning curves typically exhibited a single, large "primary" peak and often smaller, "secondary" peaks at ITDs ipsilateral and/or contralateral to the primary peak. Three indices quantified the selectivity of PA sites for ITD. The first index, which was the percent difference between the minimum and maximum response as a function of ITD, averaged 100 +/- 29%. The second index, which represented the size of the largest secondary peak relative to that of the primary peak, averaged 49 +/- 23%. The third index, which was the width of the primary ITD peak at half-maximum response, averaged only 66 +/- 35 microseconds. 6. The majority (96%; n = 192/201) of PA sites were tuned to a single "best" value of ILD. The widths of ILD tuning curves at half-maximum response averaged 24 +/- 9 dB. 7. On average, sound level had no effect on a site's best ITD or best ILD nor did it affect ITD tuning widths. ILD tuning widths did, however, tend to increase slightly with sound level (average effect was 0.1 dB ILD/dB). 8. Most PA sites responded best to contralateral-ear leading ITDs with a majority being tuned to ITDs near 0 microsecond (corresponding to sound-source locations just contralateral to the midline).(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1994NX81900026

  View details for PubMedID 7965012

• REPRESENTATION OF INTERAURAL LEVEL DIFFERENCE IN THE VLVP, THE FIRST SITE OF BINAURAL COMPARISON IN THE BARN OWLS AUDITORY-SYSTEM HEARING RESEARCH Mogdans, J., Knudsen, E. I. 1994; 74 (1-2): 148-164

  Abstract

  In the avian auditory system, the posterior division of the ventral nucleus of the lateral lemniscus (VLVp) is the first site where the levels of sound arriving at the two ears are compared. VLVp units are excited by sound at the contralateral ear and are inhibited by sound at the ipsilateral ear, and, as a result, are sensitive to interaural level differences (ILD). In this study, we investigate the functional properties of VLVp units and describe the topography of ILD sensitivity along the dorsoventral dimension of this nucleus. The responses of VLVp units were tested with monaural and binaural noise delivered through earphones. Excitatory and inhibitory responsiveness was quantified using several measures that assessed the effect of contra-ear stimulation and the effect of ipsi-ear stimulation on the contra-ear response. On the basis of these measures, we characterize the map of ILD sensitivity in the VLVp. The temporal pattern of unit responses were also analyzed. The discharges of VLVp units were regular and time-locked to the onset of a stimulus, a pattern of discharge reminiscent of the 'chopper pattern' observed in the lateral superior olive (LSO) of mammals. The temporal discharge patterns of a single VLVp neuron often distinguished between equivalent ILDs, resulting from different combinations of contra- and ipsi-ear levels, that were not distinguished by spike count alone. However, the temporal response pattern did not distinguish between all such combinations of contra- and ipsi-ear levels. The additional information was encoded by the pattern of activity across the entire population of VLVp neurons. This study describes similarities in the functional properties of VLVp and LSO units that suggest similar physiological mechanisms in avians and mammals for encoding similar acoustic information.

  View details for Web of Science ID A1994NF06500013

  View details for PubMedID 8040085

• ADAPTIVE PLASTICITY OF THE AUDITORY SPACE MAP IN THE OPTIC TECTUM OF ADULT AND BABY BARN OWLS IN RESPONSE TO EXTERNAL EAR MODIFICATION JOURNAL OF NEUROPHYSIOLOGY Knudsen, E. I., ESTERLY, S. D., Olsen, J. F. 1994; 71 (1): 79-94

  Abstract

  1. This study demonstrates the influence of experience on the establishment and maintenance of the auditory map of space in the optic tectum of the barn owl. Auditory experience was altered either by preventing the structures of the external ears (the facial ruff and preaural flaps) from appearing in baby barn owls (baby ruff-cut owls) or by removing these structures in adults (adult ruff-cut owls). These structures shape the binaural cues used for localizing sounds in both the horizontal and vertical dimensions. 2. The acoustic effects of removing the external ear structures were measured using probe tube microphones placed in the ear canals. In both baby and adult ruff-cut owls, the spatial pattern of binaural localization cues was dramatically different from normal: interaural level difference (ILD) changed with azimuth instead of with elevation, the rate of change of ILD across space was decreased relative to normal, and the rate of change of interaural time difference (ITD) across frontal space was increased relative to normal. 3. The neurophysiological representations of ITD and ILD in the optic tectum were measured before and > or = 3 mo after ruff removal in adults and beginning at 4.5 months of age in baby ruff-cut owls. Multiunit tuning to ITD and to ILD was measured using dichotic stimulation in ketamine-anesthetized owls. The tectal maps of ITD and ILD were reconstructed using visual receptive field location as a marker for recording site location in the optic tectum. 4. Adjustment of the tectal map of ITD to the altered spatial pattern of acoustic ITD was essentially complete in adults as well as in baby ruff-cut owls. This adjustment changed the magnification of ITD across the tectum, with resultant changes in ITD tuning at individual tectal sites of up to approximately 25 microseconds (approximately 5% of the physiological range) relative to normal values. 5. Adaptation of the tectal ILD map to the ruff-cut spatial pattern of acoustic ILD was substantial but clearly incomplete in both adult and baby ruff-cut owls. Although changes of up to approximately 15 dB (approximately 47% of the physiological range) relative to normal tuning were observed at certain tectal sites, the topography of the ILD map was always intermediate between normal and that predicted by the ruff-cut spatial pattern of acoustic ILD.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1994MV29500008

  View details for PubMedID 8158243

• EXPERIENCE-DEPENDENT PLASTICITY IN THE INFERIOR COLLICULUS - A SITE FOR VISUAL CALIBRATION OF THE NEURAL REPRESENTATION OF AUDITORY SPACE IN THE BARN OWL JOURNAL OF NEUROSCIENCE Brainard, M. S., Knudsen, E. I. 1993; 13 (11): 4589-4608

  Abstract

  The optic tectum (homolog of the superior colliculus) contains mutually aligned neural maps of auditory and visual space. During development, the organization of the auditory map is guided by spatial information provided by vision: barn owls raised wearing prismatic spectacles, which optically shift the visual field and the visual map in the optic tectum, develop an auditory map that is shifted by an approximately equivalent amount, such that alignment between the two maps is preserved (Knudsen and Brainard, 1991). In this study we investigated whether this shift in the auditory map is intrinsic to the optic tectum or whether it reflects plasticity at an earlier stage in the auditory pathway. Owls were raised wearing prismatic spectacles that displaced the visual field by 23 degrees to the left or right. This manipulation alters the normal correspondence between locations in the visual field and interaural time difference (ITD), the primary cue for the azimuth of a sound source. In normal owls and in owls with at least 150 d of prism experience, extracellular unit recordings were used to assess the representations of ITD at anatomically and physiologically defined sites in the optic tectum and in the two prior stages of the auditory pathway, the external and central nuclei of the inferior colliculus (ICx and ICc). In the optic tectum of normal owls, the values of ITD to which units responded most strongly (best ITDs) varied systematically with the azimuths of unit visual receptive fields (VRFs). In the prism-reared owls, best ITDs were shifted from normal toward the values of ITD produced by sounds at the locations of the units' optically displaced VRFs. In the ICx of prism-reared owls, the representation of ITD also was shifted from normal, by an amount and in a direction that could completely account for the shift in ITD measured in the optic tectum. At some sites in the ICx, the shift in ITD tuning was apparent within the first 7-8 msec of the response; shifted tuning at such short latencies argues that the altered representation of ITD in the ICx reflects plasticity in the ascending auditory pathway, and is not the result of descending activity from higher auditory centers. In the ICc, which immediately precedes the ICx in the ascending pathway, the representation of ITD was normal. The results indicate that the visual instruction of auditory spatial tuning of neurons in the optic tectum reflects plasticity at the level of the ICx, the site where the auditory map of space is first synthesized.

  View details for Web of Science ID A1993MF29700003

  View details for PubMedID 8229186

• EARLY MONAURAL OCCLUSION ALTERS THE NEURAL MAP OF INTERAURAL LEVEL DIFFERENCES IN THE INFERIOR COLLICULUS OF THE BARN OWL BRAIN RESEARCH Mogdans, J., Knudsen, E. I. 1993; 619 (1-2): 29-38

  Abstract

  Monaural occlusion during early life causes adaptive changes in the tuning of units in the owl's optic tectum to interaural level differences (ILD) that tend to align the auditory with the visual map of space. We investigated whether these changes could be due to experience-dependent plasticity occurring in the auditory pathway prior to the optic tectum. Units were recorded in the external nucleus of the inferior colliculus (ICx), which is a major source of auditory input to the optic tectum. The tuning of ICx units to ILD was measured in normal barn owls and in barn owls raised with one ear occluded. ILD tuning at each recording site was measured with dichotic noise bursts, presented at a constant average binaural level, 20 dB above threshold. The best ILD at each site was defined as the midpoint of the range of ILD values which elicited more than 50% of the maximum response. A physiological map of ILD was found in the ICx of normal owls: best ILDs changed systematically from right-ear-greater to left-ear-greater as the electrode progressed from dorsal to ventral. Best ILDs ranged from 13 dB right-ear-greater to 15 dB left-ear-greater and progressed at an average rate of 12 dB/mm. The representations of ILD were similar on both sides of the brain. In the ICx of owls raised with one ear occluded, the map of ILD was shifted in the adaptive direction: ILD tuning was shifted towards values favoring the non-occluded ear (the direction that would restore a normal space map). The average magnitude of the shift was on the order of 8-10 dB in each of 4 owls. In one owl, the mean shift in ILD tuning was almost identical on both sides of the brain. In another owl, the mean shift was much larger on the side ipsilateral to the occlusion than on the contralateral side. In both cases, the mean shifts measured in each ICx were comparable to the mean shifts measured in the optic tectum on the same sides of the brain. Thus, the adjustments in ILD tuning that have been observed in the optic tectum in response to monaural occlusion are almost entirely due to adaptive mechanisms that operate at or before the level of the ICx.

  View details for Web of Science ID A1993LQ51100004

  View details for PubMedID 8374783

• PARALLEL PATHWAYS MEDIATING BOTH SOUND LOCALIZATION AND GAZE CONTROL IN THE FOREBRAIN AND MIDBRAIN OF THE BARN OWL JOURNAL OF NEUROSCIENCE Knudsen, E. I., KNUDSEN, P. F., MASINO, T. 1993; 13 (7): 2837-2852

  Abstract

  The hypothesis that sound localization and gaze control are mediated in parallel in the midbrain and forebrain was tested in the barn owl. The midbrain pathway for gaze control was interrupted by reversible inactivation (muscimol injection) or lesion of the optic tectum. Auditory input to the forebrain was disrupted by reversible inactivation or lesion of the primary thalamic auditory nucleus, nucleus ovoidalis (homolog of the medial geniculate nucleus). Barn owls were trained to orient their gaze toward auditory or visual stimuli presented from random locations in a darkened sound chamber. Auditory and visual test stimuli were brief so that the stimulus was over before the orienting response was completed. The accuracy and kinetics of the orienting responses were measured with a search coil attached to the head. Unilateral inactivation of the optic tectum had immediate and long-lasting effects on auditory orienting behavior. The owls failed to respond on a high percentage of trials when the auditory test stimulus was located on the side contralateral to the inactivated tectum. When they did respond, the response was usually (but not always) short of the target, and the latency of the response was abnormally long. When the auditory stimulus was located on the side ipsilateral to the inactivated tectum, responses were reliable and accurate, and the latency of responses was shorter than normal. In a tectally lesioned animal, response probability and latency to contralateral sounds returned to normal within 2 weeks, but the increase in response error (due to undershooting) persisted for at least 12 weeks. Despite abnormalities in the response, all of the owls were capable of localizing and orienting to contralateral auditory stimuli on some trials with the optic tectum inactivated or lesioned. This was not true for contralateral visual stimuli. Immediately following tectal inactivation, the owls exhibited complete neglect for visual stimuli located more than 20 degrees to the contralateral side (i.e., beyond the edge of the visual field of the ipsilateral eye). In the tectally lesioned animal, this neglect diminished with time. Unilateral inactivation of nucleus ovoidalis had different effects in three owls. Response error to contralateral sound sources increased for one owl and decreased for two; response error to ipsilateral sources did not change significantly for any. The probability of response to ipsilateral (but not contralateral) stimuli decreased for one owl. The latency of response to ipsilateral (but not contralateral) stimuli increased for one and decreased for another. All of the owls, however, routinely localized and oriented toward ipsilateral and contralateral auditory stimuli with nucleus ovoidalis inactivated.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1993LM27300009

  View details for PubMedID 8331375

• ORIENTING HEAD MOVEMENTS RESULTING FROM ELECTRICAL MICROSTIMULATION OF THE BRAIN-STEM TEGMENTUM IN THE BARN OWL JOURNAL OF NEUROSCIENCE MASINO, T., Knudsen, E. I. 1993; 13 (1): 351-370

  Abstract

  The size and direction of orienting movements are represented systematically as a motor map in the optic tectum of the barn owl (du Lac and Knudsen, 1990). The optic tectum projects to several distinct regions in the medial brainstem tegmentum, which in turn project to the spinal cord (Masino and Knudsen, 1992). This study explores the hypothesis that a fundamental transformation in the neural representation of orienting movements takes place in the brainstem tegmentum. Head movements evoked by electrical microstimulation in the brainstem tegmentum of the alert barn owl were cataloged and the sites of stimulation were reconstructed histologically. Movements elicited from the brainstem tegmentum were categorized into one of six different classes: saccadic head rotations, head translations, facial movements, vocalizations, limb movements, and twitches. Saccadic head rotations could be further subdivided into two general categories: fixed-direction saccades and goal-directed saccades. Fixed-direction saccades, those whose direction was independent of initial head position, were elicited from the midbrain tegmentum. Goal-directed saccades, those whose direction changed with initial head position, were elicited from the central rhombencephalic reticular formation and from the efferent pathway of the cerebellum. Particular attention was paid to sites from which fixed-direction saccadic movements were elicited, as these movements appeared to represent components of orienting movements. Microstimulation in the medial midbrain tegmentum elicited fixed-direction saccades in one of six directions: rightward, leftward, upward, downward, clockwise roll, and counterclockwise roll. Stimulation in and around the interstitial nucleus of Cajal (InC; a complete list of anatomical abbreviations is given in the Appendix) produced ipsiversive horizontal saccades. Stimulation in the ventral InC and near the dorsal and medial edges of the red nucleus produced upward saccades. Stimulation in the reticular formation near the lateral edge of the red nucleus produced downward saccades. Stimulation in the ventromedial central gray produced ipsiversive roll saccades. The metrics and kinetics of fixed-direction saccades, but not their directions, could be influenced by stimulation parameters. As such, direction was an invariant property of the circuits being activated, whereas movement latency, duration, velocity, and size each demonstrated dependencies on stimulus amplitude, frequency, and duration. The data demonstrate directly that at the level of the midbrain tegmentum there exists a three-dimensional Cartesian representation of head-orienting movements such that horizontal, vertical, and roll components of movement are encoded by anatomically distinct neural circuits.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1993KG65900027

  View details for PubMedID 8423480

• AUDITORY LEARNING IN OWLS 7th Novo Nordisk Foundation Symposium on Memory Concepts - 1993 Brainard, M. S., Knudsen, E. I. ELSEVIER SCIENCE PUBL B V. 1993: 113–125

  View details for Web of Science ID A1993BZ58N00008

• VISUAL CALIBRATION OF THE NEURAL REPRESENTATION OF AUDITORY SPACE IN THE BARN OWL 3rd International Symposium on Dynamics of Perception Brainard, M. S., Knudsen, E. I. BIOMED RES FOUND. 1993: 35–40

  View details for Web of Science ID A1993MW68500007

• ANATOMICAL PATHWAYS FROM THE OPTIC TECTUM TO THE SPINAL-CORD SUBSERVING ORIENTING MOVEMENTS IN THE BARN OWL EXPERIMENTAL BRAIN RESEARCH MASINO, T., Knudsen, E. I. 1992; 92 (2): 194-208

  Abstract

  Electrical stimulation of the optic tectum in many vertebrate species elicits eye, head or body orienting movements in the direction of the receptive field location recorded at the site of stimulation; in the barn owl, tectal stimulation produces short latency saccadic head movements (du Lac and Knudsen 1990). However, the barn owl, like other avians, lacks a direct projection from the tectum to the spinal cord, implying that less direct connections underlie tectally mediated head movements. In order to determine the pathways by which the tectum gains access to spinal cord circuitry, we searched for overlap regions between tectal efferent projections and the locations of cells afferent to the spinal cord. Tectal efferent pathways and terminal fields were revealed by anterograde labeling using horseradish peroxidase (HRP) or tritiated amino acids injected into the optic tectum. Cells afferent to the spinal cord were identified by means of retrograde labeling using HRP, rhodamine, or rhodamine-coupled latex beads injected into the cervical spinal cord. A comparison of results from the anterograde and retrograde labeling experiments demonstrated several areas of overlap. All of the cell groups that both received heavy tectal input and contained a high proportion of cells projecting to the spinal cord were located in the medial half of the midbrain and rhombencephalic tegmentum, and included the red nucleus, the interstitial nucleus of Cajal, the medial reticular formation, the nucleus reticularis pontis giganto-cellularis, and the nucleus reticularis pontis oralis. All of these cell groups receive their tectal input from the medial efferent pathway, one of three major output pathways from the tectum. The other two output pathways (the rostral and the caudal) project to regions containing no more than a few scattered cells that are afferent to the spinal cord. Based on these data and on the functions of homologous cell groups in other vertebrates, we hypothesize that the medial efferent pathway and its brainstem target nuclei are primarily responsible for tectally mediated orienting head movements in the barn owl.

  View details for Web of Science ID A1992KC38100002

  View details for PubMedID 1493861

• ADAPTIVE ADJUSTMENT OF UNIT TUNING TO SOUND LOCALIZATION CUES IN RESPONSE TO MONAURAL OCCLUSION IN DEVELOPING OWL OPTIC TECTUM JOURNAL OF NEUROSCIENCE Mogdans, J., Knudsen, E. I. 1992; 12 (9): 3473-3484

  Abstract

  Bimodal units in the barn owl's optic tectum are tuned to the location of auditory and visual stimuli, and are systematically organized according to their spatial tuning to form mutually aligned maps of auditory and visual space. Map alignment results from the fact that, normally, units are tuned to the values of interaural level difference (ILD) and interaural time difference (ITD) produced by a sound source at the location of their visual receptive fields (VRFs). Monaural occlusion alters the correspondence of ILD and ITD values with locations in space. We investigated the effect that raising owls with a chronic monaural occlusion has on the tuning of tectal units to ILD and ITD. Owls were monaurally occluded beginning at 1 month of age. The effects of monaural occlusion were assessed 2-4 months later by comparing the ILD and ITD tuning of units in monaurally occluded owls with the ILD and ITD tuning of units with equivalent VRFs in normal owls. ILD and ITD tuning was shifted substantially and in the direction of the unoccluded ear (the adaptive direction) in owls raised with a monaural occlusion. In most tecta, the mapped representations of ILD and ITD were shifted systematically. In addition, in some tecta, monaural occlusion induced a change in the topography of the ILD map such that ILD tuning remained essentially constant at values near 0 dB over abnormally large portions of the tectum. Across all recording sites, the average shift in ILD tuning was 9 dB (n = 396) and the average shift in ITD tuning was 40 microseconds (n = 414). In four of five animals, the magnitude of the effect was not equivalent on the two sides of the brain, the adjustments being significantly larger and more systematic on the side ipsilateral to the occlusion. Such differences in the altered ILD and ITD maps on the two sides of the brain in individual animals indicate that, although a component of the adaptive adjustment might be due to regulation of the gain and phase response of the monaural signals early in the auditory pathway, a major component of the adjustment must occur at or beyond the level where the encoding of ILDs and ITDs for left and right space separates.

  View details for Web of Science ID A1992JN80700016

  View details for PubMedID 1527591

• VISION-INDEPENDENT ADJUSTMENT OF UNIT TUNING TO SOUND LOCALIZATION CUES IN RESPONSE TO MONAURAL OCCLUSION IN DEVELOPING OWL OPTIC TECTUM JOURNAL OF NEUROSCIENCE Knudsen, E. I., Mogdans, J. 1992; 12 (9): 3485-3493

  Abstract

  Neurons in the developing optic tectum adjust their tuning to auditory localization cues in response to chronic monaural occlusion so that auditory spatial fields align with visual receptive fields (VRFs). We tested whether this adaptive adjustment of auditory tuning requires visual instruction. Both eyelids were sutured closed at the same time that one ear was occluded in two barn owls that were 1 month old. After 70 and 100 d, respectively, the tuning of units to interaural level difference (ILD) and to interaural time difference (ITD) was measured. These data were compared with equivalent data from 15 normal owls. Unit tuning to ITD was shifted from normal in both of the monaurally occluded owls. In one owl, ILD tuning was also clearly shifted. In the other owl, the map of ILD was flipped upside down and adaptive adjustments in ILD tuning could not be assessed. Instead, adjustments in ILD tuning were observed following removal of the earplug with the eyelids kept closed. Unit tuning was monitored at several sites in the tectum for 1 month after earplug removal using chronically implanted electrodes. Then, ILD tuning was resampled across the entire tectum. Both measures indicated shifts in ILD tuning in response to removal of the earplug in the second blind owl. In both animals, the magnitude of the shifts in ILD tuning and ITD tuning was smaller than has been observed previously in monaurally occluded but sighted owls. The results demonstrate that the brain can make adaptive adjustments in ILD and ITD tuning in response to early monaural occlusion even without the guiding influence of vision.

  View details for Web of Science ID A1992JN80700017

  View details for PubMedID 1527592

• NEURAL DERIVATION OF SOUND SOURCE LOCATION - RESOLUTION OF SPATIAL AMBIGUITIES IN BINAURAL CUES JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA Brainard, M. S., Knudsen, E. I., ESTERLY, S. D. 1992; 91 (2): 1015-1027

  Abstract

  Cues for sound localization are inherently spatially ambiguous. Nevertheless, most neurons in the barn owl's optic tectum (superior colliculus) have receptive fields for broadband noise stimuli that are restricted to a single region of space. This study characterizes the spatial ambiguities associated with two important sets of localization cues, interaural level differences (ILDs) and interaural phase differences (IPDs), and describes how information is integrated within and across frequencies to resolve these ambiguities. The auditory receptive fields of neurons in the optic tectum were measured with free-field sounds presented from a movable loudspeaker. In contrast to the single regions typical for broadband receptive fields, receptive fields for tonal stimuli usually included additional discrete regions of space (accessory fields). Based on acoustic measurements of ILD and IPD cues made in the external ear canals, it was shown that accessory fields corresponded to locations from which sound sources produced ILD and IPD values that were approximately the same as those arising from the broadband receptive field. In addition, accessory fields had inhibitory surrounds, corresponding to locations from which sound sources produced substantially different combinations of ILD and IPD values. Where an accessory field for one frequency overlapped with the inhibitory surround of a second frequency, an excitatory response to the first frequency could be reduced or eliminated by addition of the second frequency. Because tonal receptive fields for different frequencies always overlapped in the region of the broadband receptive field but tended not to overlap elsewhere, this integration of excitation and inhibition can account for the restriction of broadband receptive fields to a single region of space.

  View details for Web of Science ID A1992HC90000045

  View details for PubMedID 1556303

• Dynamic space codes in the superior colliculus. Current opinion in neurobiology Knudsen, E. I. 1991; 1 (4): 628-632

  Abstract

  Space coding in the superior colliculus has traditionally been viewed as a static representation by multiple, aligned, sensory and motor maps. Recent evidence has revealed that the maps are dynamic, shaped by sensory experience in developing animals, and by eye and head position signals in adults. The superior colliculus thus provides an ideal model for studying the neural mechanisms underlying developmental and real-time modifications of information representation in the brain.

  View details for PubMedID 1822308

• VISUAL INSTRUCTION OF THE NEURAL MAP OF AUDITORY SPACE IN THE DEVELOPING OPTIC TECTUM SCIENCE Knudsen, E. I., Brainard, M. S. 1991; 253 (5015): 85-87

  Abstract

  Neural maps of visual and auditory space are aligned in the adult optic tectum. In barn owls, this alignment of sensory maps was found to be controlled during ontogeny by visual instruction of the auditory spatial tuning of neurons. Large adaptive changes in auditory spatial tuning were induced by raising owls with displacing prisms mounted in spectacle frames in front of the eyes; neurons became tuned to sound source locations corresponding to their optically displaced, rather than their normal, visual receptive field locations. The results demonstrate that visual experience during development calibrates the tectal auditory space map in a site-specific manner, dictating its topography and alignment with the visual space map.

  View details for Web of Science ID A1991FV17700041

  View details for PubMedID 2063209

• STRETCHED AND UPSIDE-DOWN MAPS OF AUDITORY SPACE IN THE OPTIC TECTUM OF BLIND-REARED OWLS - ACOUSTIC BASIS AND BEHAVIORAL-CORRELATES JOURNAL OF NEUROSCIENCE Knudsen, E. I., ESTERLY, S. D., DULAC, S. 1991; 11 (6): 1727-1747

  Abstract

  Vision during early life plays an important role in calibrating sound localization behavior. This study investigates the effects of visual deprivation on sound localization and on the neural representation of auditory space. Nine barn owls were raised with eyelids sutured closed; one owl was congenitally anophthalmic. Data from these birds were compared with data from owls raised with normal visual experience. Sound localization behavior was significantly less precise in blind-reared owls than in normal owls. The scatter of localization errors was particularly large in elevation, though it was abnormally large in both dimensions. However, there was no systematic bias to the localization errors measured over a range of source locations. This indicates that the representation of auditory space is degraded in some way for blind-reared owls, but on average is properly calibrated. The spatial tuning of auditory neurons in the optic tectum was studied in seven of the blind-reared owls to assess the effects of early visual deprivation on the neural representation of auditory space. In normal owls, units in the optic tectum are sharply tuned for sound source location and are organized systematically according to the locations of their receptive fields to form a map of auditory space. In blind-reared owls, the following auditory properties were abnormal: (1) auditory tuning for source elevation was abnormally broad, (2) the progression of the azimuths and elevations of auditory receptive fields across the tectum was erratic, and (3) in five of the seven owls, the auditory representation of elevation was systematically stretched, and in the two others large portions of the representation of elevation were flipped upside down. The following unit properties were apparently unaffected by blind rearing: (1) the sharpness of tuning for sound source azimuth, (2) the orientation of the auditory representation of azimuth, and (3) the mutual alignment of the auditory and visual receptive fields in the region of the tectum representing the area of space directly in front of the animal. The data demonstrate that the brain is capable of generating an auditory map of space without vision, but that the normal precision and topography of the map depend on visual experience. The space map results from the tuning of tectal units for interaural intensity differences (IIDs) and interaural time differences (ITDs; Olsen et al., 1989).(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1991FR28400023

  View details for PubMedID 2045884

• EARLY VISUAL DEPRIVATION RESULTS IN A DEGRADED MOTOR MAP IN THE OPTIC TECTUM OF BARN OWLS PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA DULAC, S., Knudsen, E. I. 1991; 88 (8): 3426-3430

  Abstract

  The optic tectum contains a precise map of orienting movements: the size and direction of movements of the eyes, head, and/or body vary systematically with the locus of neural activation within the tectum. In adult animals, this motor map aligns closely with the tectal map of visual space. This study addressed the question of whether the motor map develops entirely independently of visual experience. We found that in barn owls (Tyto alba) raised without vision, although a tectal map of head movement develops, its topography and alignment with the map of visual (and auditory) space are abnormal. The results demonstrate that during early life vision is necessary either to maintain or to guide the development of a normal tectal motor map.

  View details for Web of Science ID A1991FG91300096

  View details for PubMedID 2014263

• HORIZONTAL AND VERTICAL COMPONENTS OF HEAD MOVEMENT ARE CONTROLLED BY DISTINCT NEURAL CIRCUITS IN THE BARN OWL NATURE MASINO, T., Knudsen, E. I. 1990; 345 (6274): 434-437

  Abstract

  To generate behaviour, the brain must transform sensory information into signals that are appropriate to control movement. Sensory and motor coordinate frames are fundamentally different, however: sensory coordinates are based on the spatiotemporal patterns of activity arising from the various sense organs, whereas motor coordinates are based on the pulling directions of muscles or groups of muscles. Results from psychophysical experiments suggest that in the process of transforming sensory information into motor control signals, the brain encodes movements in abstract or extrinsic coordinate frames, that is ones not closely related to the geometry of the sensory apparatus or of the skeletomusculature. Here we show that an abstract code underlies movements of the head by the barn owl. Specifically, the data show that subsequent to the retinotopic code for space in the optic tectum yet before the motor neuron code for muscle tensions there exists a code for head movement in which upward, downward, leftward and rightward components of movement are controlled by four functionally distinct neural circuits. Such independent coding of orthogonal components of movement may be a common intermediate step in the transformation of sensation into behaviour.

  View details for Web of Science ID A1990DG08200061

  View details for PubMedID 2342573

• SENSITIVE AND CRITICAL PERIODS FOR VISUAL CALIBRATION OF SOUND LOCALIZATION BY BARN OWLS JOURNAL OF NEUROSCIENCE Knudsen, E. I., KNUDSEN, P. F. 1990; 10 (1): 222-232

  Abstract

  This study describes developmental changes in the capacity of owls to adjust sound localization in response to chronic prismatic displacement of the visual field and to recover accurate sound localization following the restoration of normal vision. Matched, binocular displacing prisms were mounted over the eyes of 19 barn owls (Tyto alba) beginning at ages ranging from 10 to 272 d. In nearly all cases, the visual field was shifted 23 degrees to the right. Sound localization was assessed on the basis of head orientations to sound sources, measured in a darkened sound chamber with a search coil system. Chronic exposure to a displaced visual field caused the owls to alter sound localization in the direction of the visual field displacement, thereby inducing a sound-localization error. The size of the sound-localization error that resulted depended on the age of the animal when prism experience began. Maximal errors of about 20 degrees were induced only when prism experience began by 21 d of age. As prism experience began at later ages, the magnitude of induced errors decreased. A bird that wore prisms beginning at 102 d of age, altered sound localization by only 6 degrees. An adult owl, when exposed chronically to a displaced visual field, altered sound localization by about 3 degrees. We refer to the early period in life when displaced vision induces exceptionally large sound-localization errors (relative to those induced in the adult) as a sensitive period. The capacity to recover accurate sound localization following restoration of normal vision was tested in 7 owls that had been raised wearing prisms. Four owls that had prisms removed by 182 d of age recovered accurate localization rapidly (over a period of weeks), whereas 3 owls that were older when the prisms were removed did not recover accurate localization when tested for up to 7 months after prism removal. Adjustment of sound localization slowed greatly or ceased at about 200 days of age, referred to here as the critical period for visual calibration of sound localization. Three owls were subjected repetitively to displacement of the visual field. An owl that adjusted sound localization to the left of normal during the sensitive period retained the capacity to adjust again to the left, but not to the right of normal, later in the critical period. The converse was true for an owl that adjusted sound localization to the right of normal during the sensitive period.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1990CL19800024

  View details for PubMedID 2299394

• NEURAL MAPS OF HEAD MOVEMENT VECTOR AND SPEED IN THE OPTIC TECTUM OF THE BARN OWL JOURNAL OF NEUROPHYSIOLOGY DULAC, S., Knudsen, E. I. 1990; 63 (1): 131-146

  Abstract

  1. This study investigates the contribution of the optic tectum in encoding the metric and kinetic properties of saccadic head movements. We describe the dependence of head movement components (size, direction, and speed) on parameters of focal electrical stimulation of the barn owl's optic tectum. The results demonstrate that both the site and the amount of activity can influence head saccade metrics and kinetics. 2. Electrical stimulation of the owl's optic tectum elicited rapid head movements that closely resembled natural head movements made in response to auditory and visual stimuli. The kinetics of these movements were similar to those of saccadic eye movements in primates. 3. The metrics and kinetics of head movements evoked from any given site depended strongly on stimulus parameters. Movement duration increased with stimulus duration, as did movement size. Both the size and the maximum speed of the movement increased to a plateau value with current strength and pulse rate. Movement direction was independent of stimulus parameters. 4. The initial position of the head influenced the size, direction, and speed of movements evoked from any given site: when the owl initially faced away from the direction of the induced saccade, the movement was larger and faster than when the owl initially faced toward the direction of the induced movement. 5. A characteristic movement of particular size, direction, and speed could be defined for each site by the use of stimulation parameters that elicited plateau movements with normal kinetic profiles and by having the head initially centered on the body. The size, direction, and speed of these characteristic movements varied systematically with the site of stimulation across the tectum. The map of head movement vector (size and direction) was aligned with the sensory representations of visual and auditory space, such that the movement elicited from a given site when the owl initially faced straight ahead brought the owl to face that region of space represented by the sensory responses of the neurons at the site of stimulation. 6. The results imply that both the site and the amount of neural activity in the optic tectum contribute to encoding the metrics and kinetics of saccadic movements. A comparison of the present findings with previous studies on saccadic eye movements in primates and combined eye and head movements in cats suggests striking similarities in the ways in which tectal activity specifies a redirection in gaze to such dissimilar motor effectors as the eyes and head.

  View details for Web of Science ID A1990CJ01600010

  View details for PubMedID 2299378

• VISION CALIBRATES SOUND LOCALIZATION IN DEVELOPING BARN OWLS JOURNAL OF NEUROSCIENCE Knudsen, E. I., KNUDSEN, P. F. 1989; 9 (9): 3306-3313

  Abstract

  This study demonstrates that continuous exposure of baby barn owls to a displaced visual field causes a shift in sound localization in the direction of the visual displacement. This implies an innate dominance of vision over audition in the development and maintenance of sound localization. Twelve owls were raised from the first day of eye opening wearing binocular prisms that displaced the visual field to the right by 11 degrees, 23 degrees, or 34 degrees. The prisms were worn for periods of up to 7 months. Consistent with previous results (Knudsen and Knudsen, 1989a), owls reared with displacing prisms did not adjust head orientation to visual stimuli. While wearing prisms, owls consistently oriented the head to the right of visual targets, and, as soon as the prisms were removed, they oriented the head directly at visual targets, as do normal owls. In contrast, prism-reared owls did change head orientation to sound sources even though auditory cues were not altered significantly. Birds reared wearing 11 degrees or 23 degrees prisms oriented the head to the right of acoustic targets by an amount approximately equal to the optical displacement induced by the prisms. Birds raised wearing 34 degrees prisms adjusted sound localization by only about 50% of the optical displacement. Thus, visually guided adjustment of sound localization appears to be limited to about 20 degrees in azimuth. The data indicate that when confronted with consistently discordant localization information from the auditory and visual systems, developing owls use vision to calibrate associations of auditory localization cues with locations in space in an attempt to bring into alignment the perceived locations of auditory and visual stimuli emanating from a common source. Vision exerts this instructive influence on sound localization whether or not visual information is accurate.

  View details for Web of Science ID A1989AT43400025

  View details for PubMedID 2795164

• VISUOMOTOR ADAPTATION TO DISPLACING PRISMS BY ADULT AND BABY BARN OWLS JOURNAL OF NEUROSCIENCE Knudsen, E. I., KNUDSEN, P. F. 1989; 9 (9): 3297-3305

  Abstract

  The capacity of barn owls to adapt visuomotor behavior in response to prism-induced displacement of the visual field was tested in babies and adults. Matched, binocular Fresnel prisms, which displaced the visual field 11 degrees, 23 degrees, or 34 degrees to the right, were placed on owls for periods of up to 99 d. Seven baby owls wore the prisms from the day the eyelids first opened; 2 owls wore them as adults. Prism adaptation was measured by the accuracy with which a target was approached and struck with the talons, a behavior similar to pointing behavior used commonly to assess prism adaptation in primates. Baby and adult owls exhibited a limited capacity to adapt this visuomotor behavior. Acquisition of adapted behavior was slow, taking place over a period of weeks, and was never complete even for owls that were raised viewing the world through relatively weak (11 degrees) displacing prisms. When the prisms were removed from adapted owls, they struck to the opposite side of the target. The recovery of strike accuracy following prism removal was rapid; 7 of 9 owls recovered normal accuracy within 30 min of prism removal, despite having worn the prisms for months. This limited capacity for adaptation contrasts dramatically with the extensive and rapid adaptation exhibited by adult primates exposed to comparable prismatic displacements. The mechanism of adaptation used by the owls was to alter the movements employed for approaching targets. Instead of moving straight ahead, the head and body moved diagonally relative to the orientation of the head. Thus, in contrast to prism adaptation by humans that can involve reinterpretation of eye, head, and limb position, prism adaptation by owls is based on changes in the motor commands that underlie approach behavior.

  View details for Web of Science ID A1989AT43400024

  View details for PubMedID 2795163

• NEURAL MAPS OF INTERAURAL TIME AND INTENSITY DIFFERENCES IN THE OPTIC TECTUM OF THE BARN OWL JOURNAL OF NEUROSCIENCE Olsen, J. F., Knudsen, E. I., ESTERLY, S. D. 1989; 9 (7): 2591-2605

  Abstract

  This report describes the binaural basis of the auditory space map in the optic tectum of the barn owl (Tyto alba). Single units were recorded extracellularly in ketamine-anesthetized birds. Unit tuning for interaural differences in timing and intensity of wideband noise was measured using digitally synthesized sound presented through earphones. Spatial receptive fields of the same units were measured with a free field sound source. Auditory units in the optic tectum are sharply tuned for both the azimuth and the elevation of a free field sound source. To determine the binaural cues that could be responsible for this spatial tuning, we measured in the ear canals the amplitude and phase spectra produced by a free field noise source and calculated from these measurements the interaural differences in time and intensity associated with each of 178 locations throughout the frontal hemisphere. For all frequencies, interaural time differences (ITDs) varied systematically and most strongly with source azimuth. The pattern of variation of interaural intensity differences (IIDs) depended on frequency. For low frequencies (below 4 kHz) IID varied primarily with source azimuth, whereas for high frequencies (above 5 kHz) IID varied primarily with source elevation. Tectal units were tuned for interaural differences in both time and intensity of dichotic stimuli. Changing either parameter away from the best value for the unit decreased the unit's response. The tuning of units to either parameter was sharp: the width of ITD tuning curves, measured at 50% of the maximum response with IID held constant (50% tuning width), ranged from 18 to 82 microsecs. The 50% tuning widths of IID tuning curves, measured with ITD held constant, ranged from 8 to 37 dB. For most units, tuning for ITD was largely independent of IID, and vice versa. A few units exhibited systematic shifts of the best ITD with changes in IID (or shifts of the best IID with changes in ITD); for these units, a change in the value of one parameter to favor one ear shifted the best value of the other parameter in favor of the same ear, i.e., in the direction opposite to that expected from "time-intensity trading." Overall sound intensity had little or no effect on ITD tuning, but did increase the best IIDs of units tuned to nonzero IIDs. The tuning of units for ITD and IID changed systematically along different dimensions of the optic tectum to create coextensive, independent neurophysiological maps of ITD and IID.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1989AG11500034

  View details for PubMedID 2746340

• FUSED BINOCULAR VISION IS REQUIRED FOR DEVELOPMENT OF PROPER EYE ALIGNMENT IN BARN OWLS VISUAL NEUROSCIENCE Knudsen, E. I. 1989; 2 (1): 35-40

  Abstract

  The eyes of adult barn owls (Tyto alba) are virtually fixed in the head in positions that are highly consistent from one individual to the next. However, early in development the eyes are exodeviated; the eyes achieve their adult positions during the owl's second month of life. Disruption of binocular vision in baby owls leads to permanent, highly abnormal eye positions and interocular alignment. Of three owls raised with both eyelids sutured closed, two developed exotropic strabismus and one developed esotropic strabismus. Two owls reared with monocular vision developed esotropic strabismus, whereas three owls reared with fused, but optically deviated binocular vision developed normal eye positions. Thus, the alignment of the eyes in adults results from an active process that depends on fused binocular vision during early life. Extracellular microelectrode recordings from the optic tecta of strabismic owls reveal that many units retain binocular inputs from corresponding points of the two eyes: the left-eye and right-eye receptive fields of individual units are misaligned by an amount predicted by the direction and magnitude of the strabismus. These results indicate that an innately determined pattern of connections in the brain anticipates the eye positions necessary to achieve binocular fusion. The hypothesis is put forth that the powerful activation of such binocular neurons by strong, synchronous inputs from the two eyes is the signal required by the optimotor system that proper eye alignment has been attained.

  View details for Web of Science ID A1989T223100006

  View details for PubMedID 2487636

• EARLY BLINDNESS RESULTS IN A DEGRADED AUDITORY MAP OF SPACE IN THE OPTIC TECTUM OF THE BARN OWL PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Knudsen, E. I. 1988; 85 (16): 6211-6214

  Abstract

  The optic tectum of the barn owl (Tyto alba) contains a neural map of auditory space consisting of neurons that are sharply tuned for sound source location and organized precisely according to their spatial tuning. The importance of vision for the development of this auditory map was investigated by comparing space maps measured in normal owls with those measured in owls raised with both eyelids sutured closed. The results demonstrate that owls raised without sight, but with normal hearing, develop auditory space maps with degraded precision and with aspects of topography that are abnormal.

  View details for Web of Science ID A1988P781800092

  View details for PubMedID 3413089

• NEURAL DERIVATION OF SOUND SOURCE LOCATION IN THE BARN OWL - AN EXAMPLE OF A COMPUTATIONAL MAP ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Knudsen, E. I. 1987; 510: 33-38

  View details for Web of Science ID A1987R094800006

  View details for PubMedID 3324875

• CHANGES IN EXTERNAL EAR POSITION MODIFY THE SPATIAL TUNING OF AUDITORY UNITS IN THE CATS SUPERIOR COLLICULUS JOURNAL OF NEUROPHYSIOLOGY Middlebrooks, J. C., Knudsen, E. I. 1987; 57 (3): 672-687

  Abstract

  This study examines the influence of external ear position on the auditory spatial tuning of single units in the superior colliculus of the anesthetized cat. Unit responses to broad-band stimuli presented in a free sound field were measured with the external ears in a forward symmetrical position or with one or the other ear turned 40 degrees to the side; the ears are referred to as contra- or ipsilateral with respect to the side of the recording site. Changes in the position of either ear modified the spatial tuning of units. The region of space from which a stimulus was most effective in activating a unit is referred to as the unit's "best area". Whenever the contralateral ear was turned to the side, best areas shifted peripherally and somewhat upward, roughly in proportion to the magnitude of the change in ear position. A turn of the ipsilateral ear to the side had more variable effects, but best areas generally shifted frontally. Best areas located between approximately 10 and 40 degrees contralateral when the ears were forward were least affected by changes in ipsilateral ear position. Changes in ear position also modified the maximum response rates of many units. Units with best areas located within approximately 20 degrees of the frontal midline when the ears were forward exhibited a pronounced decrease in responsiveness when either ear was turned. Units with more peripheral best areas tended to show no change or a slight increase in responsiveness. The influence of ear position on the directionality of the external ears was determined by mapping the cochlear microphonic response to tones or one-third-octave bands of noise before and after turning the ear. When the ears were forward, maximum interaural intensity differences (IIDs) were produced by high-frequency sound sources (greater than or equal to 20 kHz) located 20-40 degrees from the frontal midline and by lower frequency sources located further peripherally. The influence of ear position on the locations from which maximum IIDs were produced was similar to the influence of ear position on unit best areas. Changes in ipsilateral ear position had different effects on high- and low-frequency IIDs that were comparable with the effects of changes in ear position on frontally and peripherally located best areas, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1987G461100006

  View details for PubMedID 3559696

• COMPUTATIONAL MAPS IN THE BRAIN ANNUAL REVIEW OF NEUROSCIENCE Knudsen, E. I., DULAC, S., ESTERLY, S. D. 1987; 10: 41-65

  Abstract

  The nervous system performs computations to process information that is biologically important. Some of these computations occur in maps--arrays of neurons in which the tuning of neighboring neurons for a particular parameter value varies systematically. Computational maps transform the representation of information into a place-coded probability distribution that represents the computed values of parameters by sites of maximum relative activity. Numerous computational maps have been discovered, including visual maps of line orientation and direction of motion, auditory maps of amplitude spectrum and time interval, and motor maps of orienting movements. The construction of the auditory map of space is the most thoroughly understood: information about interaural delays and interaural intensity differences is processed in parallel by separate computational maps, and the outputs of these maps feed into a higher order processor that integrates sets of cues corresponding to sound source locations and creates a map of auditory space. Computational maps represent ranges of parameter values that are relevant to the animal, and may differentially magnify the representation of values that are of particular importance. The tuning of individual neurons for values of a mapped parameter is broad relative to the range of the map. Consequently, neurons throughout a large portion of a computational map are activated by any given stimulus, and precise information about the mapped parameter is coded by the locations of peak activity. There are a number of advantages of performing computations in maps. First, information is processed rapidly because the computations are preset and are executed in parallel. Second, maps simplify the schemes of connectivity required for processing and utilizing the information. Third, a common, mapped representation of the results of different kinds of computations allows the nervous system to employ a single strategy for reading the information. Finally, maps enable several classes of neuronal mechanisms to sharpen tuning in a manner not possible for information that is represented in a non-topographic code.

  View details for Web of Science ID A1987G188900003

  View details for PubMedID 3551761

• THE SENSITIVE PERIOD FOR AUDITORY LOCALIZATION IN BARN OWLS IS LIMITED BY AGE, NOT BY EXPERIENCE JOURNAL OF NEUROSCIENCE Knudsen, E. I., KNUDSEN, P. F. 1986; 6 (7): 1918-1924

  Abstract

  Early in life, the barn owl passes through a sensitive period during which it can interpret and make use of abnormal auditory cues for accurate sound localization. This capacity is lost at about 8 weeks of age, just after the head and ears reach adult size (knudsen et al. 1984a). The end of the sensitive period could be triggered either by an age-dependent process or by the exposure of the auditory system to stable or adult-like cues. To distinguish between these alternatives, we subjected baby owls to constant abnormal cues (chronic monaural occlusion) or to frequently changing abnormal cues (alternating monaural occlusion) throughout the sensitive period. In the first group of animals (n = 2), one ear was plugged continuously until 73 or 79 d of age, respectively, and then the earplug was switched to the opposite ear. Although these animals adjusted sound localization accuracy during the initial chronic monaural occlusion, they could not localize sounds at all after the earplug was switched to the opposite ear, and they remained unable to localize sounds as long as the opposite ear remained occluded (7 and 27 weeks, respectively). When the second monaural occlusion was finally removed, both birds localized sounds with errors that were similar to the errors they exhibited immediately after removal of the first monaural occlusion. One bird that was 127-d-old at the time the second earplug was removed corrected its localization error; the other bird, 250-d-old when the second earplug was removed, did not.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1986D180200008

  View details for PubMedID 3734867

• VISION GUIDES THE ADJUSTMENT OF AUDITORY LOCALIZATION IN YOUNG BARN OWLS SCIENCE Knudsen, E. I., KNUDSEN, P. F. 1985; 230 (4725): 545-548

  Abstract

  Barn owls raised with one ear plugged make systematic errors in auditory localization when the earplug is removed. Young owls correct their localization errors within a few weeks. However, such animals did not correct their auditory localization errors when deprived of vision. Moreover, when prisms were mounted in front of their eyes, they adjusted their auditory localization to match the visual error induced by the prisms, as long as the visual and auditory errors were within the same quadrant of directions. The results demonstrate that, during development, the visual system provides the spatial reference for fine-tuning auditory localization.

  View details for Web of Science ID A1985ASW2500029

  View details for PubMedID 4048948

• EXPERIENCE ALTERS THE SPATIAL TUNING OF AUDITORY UNITS IN THE OPTIC TECTUM DURING A SENSITIVE PERIOD IN THE BARN OWL JOURNAL OF NEUROSCIENCE Knudsen, E. I. 1985; 5 (11): 3094-3109

  Abstract

  The auditory spatial tuning of bimodal (auditory-visual) units in the optic tectum of the barn owl was altered by raising animals with one ear occluded. Changes in spatial tuning were assessed by comparing the location of a unit's auditory best area with that of its visual receptive field. As shown previously, auditory best areas are aligned with visual receptive fields in the tecta of normal birds (Knudsen, E. I. (1982) J. Neurosci. 2: 1177-1194). It was demonstrated in this study that, when birds were raised with one ear occluded, best areas and visual receptive fields were aligned only as long as the earplug was in place. When the earplug was removed, best areas and visual receptive fields became misaligned, indicating that a change in auditory spatial tuning had taken place during the period of occlusion. However, in a bird that received an earplug as an adult, no such alterations in auditory spatial tuning were observed; even after 1 year of monaural occlusion, auditory best areas and visual receptive fields were misaligned so long as the earplug was in place, and were aligned when the earplug was removed. These results suggest that exposure to abnormal localization cues modifies the auditory spatial tuning of tectal units only during a restricted, sensitive period early in development. After the earplug was removed from a juvenile bird that had been raised with an occluded ear, the initial misalignment between auditory best areas and visual receptive fields decreased gradually over a period of weeks. In contrast, when earplugs were removed from two adult birds that had been raised with monaural occlusions, auditory-visual misalignments persisted for as long as measurements were made, which was up to 1 year after earplug removal. These data indicate that auditory cues become permanently associated with locations in visual space during a critical period which draws to a close at about the age when the animal reaches adulthood. Horseradish peroxidase was injected into two optic tecta (in a single animal) that contained units with permanently altered auditory spatial tuning. The positions of retrogradely labeled cells in the external nucleus of the inferior colliculus (ICX) were the same as those observed in control birds (Knudsen, E. I., and P. F. Knudsen (1983) J. Comp. Neurol. 218: 187-196). Thus, the changes in spatial tuning were not due to a shift in the topographic projection from the ICX to the optic tectum.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1985ATZ4900031

  View details for PubMedID 4056865

• A CRITICAL PERIOD FOR THE RECOVERY OF SOUND LOCALIZATION ACCURACY FOLLOWING MONAURAL OCCLUSION IN THE BARN OWL JOURNAL OF NEUROSCIENCE Knudsen, E. I., KNUDSEN, P. F., ESTERLY, S. D. 1984; 4 (4): 1012-1020

  Abstract

  We studied the ability of barn owls to recover accurate sound localization after being raised with one ear occluded. Most of the owls had ear plugs inserted before they reached adult size, and therefore they never experienced normal adult localization cues until their ear plugs were removed. Upon removal of their ear plugs, these owls exhibited large systematic sound localization errors. The rate at which they recovered accurate localization decreased with the age of the bird at the time of plug removal, and recovery essentially ceased when owls reached 38 to 42 weeks of age. We interpret this age as the end of a critical period for the consolidation of associations between auditory cues and locations in space. Owls that had experienced adult localization cues for a short period of time before ear plugging recovered normal accuracy rapidly, even if they remained plugged well past the end of the critical period. This suggests that a brief exposure to normal adult cues early in the critical period is sufficient to enable the recovery of localization accuracy much later in life.

  View details for Web of Science ID A1984SP46000012

  View details for PubMedID 6716128

• A NEURAL CODE FOR AUDITORY SPACE IN THE CATS SUPERIOR COLLICULUS JOURNAL OF NEUROSCIENCE Middlebrooks, J. C., Knudsen, E. I. 1984; 4 (10): 2621-2634

  Abstract

  We have examined the intermediate and deep layers of the cat's superior colliculus for evidence of a neural representation of auditory space. We measured the responses of single units to sounds presented in a free field. The results support the following generalizations. Most auditory units in the superior colliculus have sharply delimited receptive fields which form two discrete classes distinguished by their locations and sizes. The remaining units respond to sounds presented at any location. Each auditory unit responds maximally to sounds at a particular horizontal and vertical location within its receptive field, the unit's "best area." The best areas and receptive field borders of a unit are resistant to changes in the intensity of stimulus. The locations of best areas shift systematically as a function of unit position to form a continuous map of auditory space. The horizontal dimension of space is mapped rostrocaudally, and the vertical dimension is mapped mediolaterally. This map corresponds in orientation with the map of visual space. These data permit us to infer the distribution of unit activity elicited by a sound at any given location. Regardless of its location, a sound activates a substantial portion of the superior colliculus. Indeed, sounds at some locations activate nearly all of the auditory units. However the activated portion of the colliculus contains a restricted region of units which are excited to near their maximum firing rates. The position of this focus of greatest activity varies systematically according to the location of the sound source, thus mapping the location of the sound in space.

  View details for Web of Science ID A1984TN29200021

  View details for PubMedID 6491727

• AUDITORY PROPERTIES OF SPACE-TUNED UNITS IN OWLS OPTIC TECTUM JOURNAL OF NEUROPHYSIOLOGY Knudsen, E. I. 1984; 52 (4): 709-723

  Abstract

  Auditory units in the optic tectum of the barn owl (Tyto alba) were studied under free-field conditions with a movable sound source. These units are selective for sound location and their spatial tuning varies systematically across the tectum, forming a map of space (8). I found that frequency tuning, response latencies, and thresholds of units changed in parallel with their spatial tuning, suggesting that as a consequence these properties also are topographically distributed in the optic tectum. Response rates were determined primarily by the location of the sound source. Regardless of sound intensity, only stimuli delivered from a restricted "best area" elicited vigorous responses. Minimum response latencies were shortest for units with frontal best areas and increased systematically for units with best areas located more peripherally. The response latencies of units with best areas centered within 25 degrees of the owl's visual axis were virtually independent of sound intensity and speaker position. The latencies of units with more peripheral best areas varied with speaker position and were shortest when the speaker was in the best area. Thresholds to noise stimuli were lowest for units with best areas directly in front of the owl and increased systematically for units with best areas located more peripherally. Thus, in the representation of frontal space, where units have the smallest receptive fields and the magnification of space is the greatest (8), units also respond to the weakest sound fields. Many units (20%) could not be driven with tonal stimuli; of those that could, most were broadly tuned for frequency. Characteristic frequencies and high-frequency cutoffs shifted lower as best areas moved peripherally. High-frequency tones, which excited units with frontal best areas, either inhibited or failed to drive units with peripheral best areas. These systematic changes in unit response properties influence how sounds from different locations are represented in the tectum and reflect integrative strategies used by the owl's auditory system in deriving a representation of auditory space.

  View details for Web of Science ID A1984TM49300008

  View details for PubMedID 6491713

• THE ROLE OF AUDITORY EXPERIENCE IN THE DEVELOPMENT AND MAINTENANCE OF SOUND LOCALIZATION TRENDS IN NEUROSCIENCES Knudsen, E. I. 1984; 7 (9): 326-330

  View details for Web of Science ID A1984TN38000011

• MONAURAL OCCLUSION ALTERS SOUND LOCALIZATION DURING A SENSITIVE PERIOD IN THE BARN OWL JOURNAL OF NEUROSCIENCE Knudsen, E. I., ESTERLY, S. D., KNUDSEN, P. F. 1984; 4 (4): 1001-1011

  Abstract

  Sound localization was disrupted in young barn owls by chronically plugging one ear. Owls that were younger than 8 weeks of age at the time of ear plugging recovered normal localization accuracy while plugged, whereas those that were older than 8 weeks at the time of ear plugging did not. The end of the sensitive period for the adjustment of sound localization accuracy coincides with the maturation of the head and ears, suggesting that the exposure of the auditory system to stable, adult-like acoustic cues could play a role in bringing the sensitive period to a close. The results demonstrate that, early in development, associations between auditory cues and locations in space can be altered by experience.

  View details for Web of Science ID A1984SP46000011

  View details for PubMedID 6716127

• SPACE-MAPPED AUDITORY PROJECTIONS FROM THE INFERIOR COLLICULUS TO THE OPTIC TECTUM IN THE BARN OWL (TYTO-ALBA) JOURNAL OF COMPARATIVE NEUROLOGY Knudsen, E. I., KNUDSEN, P. F. 1983; 218 (2): 187-196

  Abstract

  The optic tectum of the owl contains a topographic representation of auditory space. We have investigated the source of this space-mapped auditory activity by using retrograde tracing with horseradish peroxidase. The major source of auditory input to the optic tectum is the ipsilateral external nucleus of the inferior colliculus (ICX), which is known to contain a map of auditory space also. Additional minor projections originate in the superficial nucleus of the inferior colliculus and the nucleus isthmi parvocellularis. There is no apparent projection to the optic tectum from the contralateral ICX or any other brainstem auditory nucleus. The projection from the ICX to the optic tectum is point-to-point: rostral ICX projects to rostral tectum, caudal ICX to caudal tectum, dorsal ICX to dorsomedial tectum, and ventral ICX to ventral tectum. Thus, the space-mapped organization that exists in the ICX is passed on by topographic projections to the optic tectum.

  View details for Web of Science ID A1983RA96500005

  View details for PubMedID 6886071

• SUBDIVISIONS OF THE INFERIOR COLLICULUS IN THE BARN OWL (TYTO-ALBA) JOURNAL OF COMPARATIVE NEUROLOGY Knudsen, E. I. 1983; 218 (2): 174-186

  Abstract

  The inferior colliculus in the barn owl contains three subdivisions: the central (ICC), external (ICX), and superficial (ICS) nuclei. The nuclei are distinguished on the basis of their cyto- and myeloarchitecture, connectivity, and physiological properties. The ICC may be further divided into dorsal (ICCd) and ventral (ICCv) parts. Auditory fibers ascending in the lateral lemniscus enter the ICCd and ICCv, but not the ICX or ICS. The ICX receives its auditory input from the ICC. The ICC and ICX in owls are similar in position, anatomy, connectivity, and physiology to the ICC and ICX in mammals, suggesting that these structures are homologous. Units in the ICC are organized tonotopically, whereas units in the ICX are organized according to the locations of their spatial receptive fields. This implies that a transformation from a tonotopic to a spatiotopic organization takes place in the ICX of the owl.

  View details for Web of Science ID A1983RA96500004

  View details for PubMedID 6886070

• EARLY AUDITORY EXPERIENCE ALIGNS THE AUDITORY MAP OF SPACE IN THE OPTIC TECTUM OF THE BARN OWL SCIENCE Knudsen, E. I. 1983; 222 (4626): 939-942

  Abstract

  Auditory and visual space are mapped in the optic tectum of the barn owl. Normally, these maps of space are in close mutual alignment. Ear plugs inserted unilaterally in young barn owls disrupted the binaural cues that constitute the basis of the auditory map. Yet when recordings were made from the tecta of these birds as adults, the auditory and visual maps were in register. When the ear plugs were removed from these adult birds and binaural balance was restored, the auditory maps were shifted substantially relative to the visual maps and relative to the physical borders of the tecta. These results demonstrate that the neural connectivity that gives rise to the auditory map of space in the optic tectum can be modified by experience in such a way that spatial alignment between sensory modalities is maintained.

  View details for Web of Science ID A1983RQ99000036

  View details for PubMedID 6635667

• EARLY AUDITORY EXPERIENCE MODIFIES SOUND LOCALIZATION IN BARN OWLS NATURE Knudsen, E. I., KNUDSEN, P. F., ESTERLY, S. D. 1982; 295 (5846): 238-240

  View details for Web of Science ID A1982MY42000044

• AUDITORY AND VISUAL MAPS OF SPACE IN THE OPTIC TECTUM OF THE OWL JOURNAL OF NEUROSCIENCE Knudsen, E. I. 1982; 2 (9): 1177-1194

  Abstract

  The receptive field properties and functional organization of visual and auditory responses were studied in the optic tectum of the barn owl (Tyto alba). Most units throughout the depth of the tectum responded to both visual and auditory stimuli. The entire visual field of each eye was represented topographically in the contralateral tectum. In the portion of the tectal map representing the zone of binocular vision, 50% of the superficial layer units and 100% of the deep; layer units were driven binocularly. The representation of the frontal binocular region of space was greatly expanded in the map; the average magnification factor was 3 times greater for the frontal binocular zone than for the monocular zone. The responses of the superficial and deep tectal units to auditory stimuli were space specific; they responded only when a sound source was located in a particular region of space, or receptive field, regardless of the intensity or type of sound used. Most auditory receptive fields contained a distinct "best area" where a sound source was most effective in driving the unit. Auditory space, as defined by receptive fields and best areas, was represented topographically in the tectum. The auditory and visual maps of space had the same orientations, positions, magnification factors, and termination coordinates at the anterior and dorsal edges of the tectum. Yet the maps lost their registry near the posterior and ventral margins where the most peripheral regions of space were represented. These characteristics suggest that the spatiotopic organization in the tectum is a compromise between a tendency for the space representations of different modalities to align and for the representation of each modality to fill the entire tectum.

  View details for Web of Science ID A1982PL73700001

  View details for PubMedID 7119872

• THE HEARING OF THE BARN OWL SCIENTIFIC AMERICAN Knudsen, E. I. 1981; 245 (6): 113-?

  View details for Web of Science ID A1981MR24300006