Bio

Academic Appointments


Administrative Appointments


  • Associate Dean, Office of Diversity and Leadership (2012 - Present)

Honors & Awards


  • EJLB Foundation Scholar, EJLB Foundation (2004)
  • Terman Fellow, Stanford University (1999)
  • Klingenstein Fellow, Klingenstein Foundation (1999)
  • McKnight Scholar, McKnight Endowment Fund for Neuroscience (1999)
  • Sloan Fellow, Alfred P. Sloan Foundation (1999)

Professional Education


  • Ph.D., U Texas, Houston, Neuroscience (1993)
  • B.A., Williams College, Mathematics (1987)

Research & Scholarship

Current Research and Scholarly Interests


My laboratory studies the neural mechanisms of learning. Our research aims to develop an integrated understanding of this fundamental brain function by systematically tracing learning from a sensory experience, through the neural encoding of that experience, to the induction of plasticity at specific loci in the brain, and the ultimate readout of the memory in an altered behavior. Toward this goal, we use a combination of behavioral, neurophysiological and computational approaches.

The model system we study is a form of learning that calibrates the amplitude of eye movements produced by the vestibuloocular reflex (VOR). As an experimental system, learning in the VOR offers many advantages: the neural circuitry mediating the behavior is well understood, putative sites of synaptic plasticity have been identified, and a key neural structure is the cerebellum, which is well suited for both in vivo and in vitro studies of the mechanisms of learning.

One current focus in the lab is to record from the cerebellum in awake behaving animals during the induction of learning in order to identify the neural "error signals" that detect a miscalibration in the VOR and trigger the neural changes underlying learning. Another current project is to study learning in the VOR of transgenic mice, as a tool for linking systems level analysis of learning with cellular and molecular analyses of synaptic plasticity.

Teaching

2013-14 Courses


Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


  • Cerebellar Purkinje cell activity drives motor learning. Nature neuroscience Nguyen-Vu, T. D., Kimpo, R. R., Rinaldi, J. M., Kohli, A., Zeng, H., Deisseroth, K., Raymond, J. L. 2013; 16 (12): 1734-1736

    Abstract

    The climbing fiber input to the cerebellar cortex is thought to provide instructive signals that drive the induction of motor skill learning. We found that optogenetic activation of Purkinje cells, the sole output neurons of the cerebellar cortex, can also drive motor learning in mice. This dual control over the induction of learning by climbing fibers and Purkinje cells can expand the learning capacity of motor circuits.

    View details for DOI 10.1038/nn.3576

    View details for PubMedID 24162651

  • Sexist attitudes: Most of us are biased. Nature Raymond, J. 2013; 495 (7439): 33-34

    View details for DOI 10.1038/495033a

    View details for PubMedID 23467152

  • Motor Learning Reduces Eye Movement Variability through Reweighting of Sensory Inputs JOURNAL OF NEUROSCIENCE Guo, C. C., Raymond, J. L. 2010; 30 (48): 16241-16248

    Abstract

    Motor learning can improve both the accuracy and precision of motor performance. We analyzed changes in the average trajectory and the variability of smooth eye movements during motor learning in rhesus monkeys. Training with a compound visual-vestibular stimulus could reduce the variability of the eye movement responses without altering the average responses. This improvement of eye movement precision was achieved by shifting the reliance of the movements from a more variable, visual signaling pathway to a less variable, vestibular signaling pathway. Thus, cerebellum-dependent motor learning can improve the precision of movements by reweighting sensory inputs with different variability.

    View details for DOI 10.1523/JNEUROSCI.3569-10.2010

    View details for Web of Science ID 000284999900018

    View details for PubMedID 21123570

  • Elimination of climbing fiber instructive signals during motor learning NATURE NEUROSCIENCE Ke, M. C., Guo, C. C., Raymond, J. L. 2009; 12 (9): 1171-U23

    Abstract

    The climbing fiber input to the cerebellum from the inferior olive is thought to act as a teacher whose activity controls the induction of motor learning. We designed training conditions that did not elicit instructive signals in the climbing fibers, but nevertheless induced robust and consistent motor learning in the vestibulo-ocular reflex of rhesus monkeys. Our results indicate that instructive signals in the climbing fibers are not necessary for cerebellum-dependent learning. Instead, instructive signals carried by either the climbing fibers or Purkinje cell simple spikes may be sufficient to induce motor learning, with additive effects occurring when both instructive signals are present during training.

    View details for DOI 10.1038/nn.2366

    View details for Web of Science ID 000269317300020

    View details for PubMedID 19684593

  • Disruption of Learned Timing in P/Q Calcium Channel Mutants PLOS ONE Katoh, A., Chapman, P. J., Raymond, J. L. 2008; 3 (11)

    Abstract

    To optimize motor performance, both the amplitude and temporal properties of movements should be modifiable by motor learning. Here we report that the modification of movement timing is highly dependent on signaling through P/Q-type voltage-dependent calcium channels. Two lines of mutant mice heterozygous for P/Q-type voltage-dependent calcium channels exhibited impaired plasticity of eye movement timing, but relatively intact plasticity of movement amplitude during motor learning in the vestibulo-ocular reflex. The results thus demonstrate a distinction between the molecular signaling pathways regulating the timing versus amplitude of movements.

    View details for DOI 10.1371/journal.pone.0003635

    View details for Web of Science ID 000265134300005

    View details for PubMedID 18982062

  • Impaired motor learning in the vestibulo-ocular reflex in mice with multiple climbing fiber input to cerebellar Purkinje cells JOURNAL OF NEUROSCIENCE Kimpo, R. R., Raymond, J. L. 2007; 27 (21): 5672-5682

    Abstract

    A unique feature of the cerebellar architecture is that Purkinje cells in the cerebellar cortex each receive input from a single climbing fiber. In mice deficient in the gamma isoform of protein kinase C (PKCgamma-/- mice), this normal architecture is disrupted so that individual Purkinje cells receive input from multiple climbing fibers. These mice have no other known abnormalities in the cerebellar circuit. Here, we show that PKCgamma-/- mice are profoundly impaired in vestibulo-ocular reflex (VOR) motor learning. The PKCgamma-/- mice exhibited no adaptive increases or decreases in VOR gain at training frequencies of 2 or 0.5 Hz. This impairment was present across a broad range of peak retinal slip speeds during training. We compare the results for VOR motor learning with previous studies of the performance of PKCgamma-/- mice on other cerebellum-dependent learning tasks. Together, the results suggest that single climbing fiber innervation of Purkinje cells is critical for some, but not all, forms of cerebellum-dependent learning, and this may depend on the region of the cerebellum involved, the organization of the relevant neural circuits downstream of the cerebellar cortex, as well as the timing requirements of the learning task.

    View details for DOI 10.1523/JNEUROSCI.0801-07.2007

    View details for Web of Science ID 000246720700015

    View details for PubMedID 17522312

  • Motor deficits in homozygous and heterozygous P/Q-type calcium channel mutants JOURNAL OF NEUROPHYSIOLOGY Katoh, A., Jindal, J. A., Raymond, J. L. 2007; 97 (2): 1280-1287

    Abstract

    P/Q-type voltage-dependent Ca(2+) channels (VDCCs) are highly expressed in the cerebellum, and mutations of these channels are associated with disrupted motor function. Several allelic variants of the alpha1A pore-forming subunit of P/Q-type VDCCs have been described, and mice homozygous for these mutations exhibit gait ataxia, as do alpha1A knockout mice. Here we report that heterozygous alpha1A mutants also have a motor phenotype. Mice heterozygous for the leaner and alpha1A knockout mutations exhibit impaired motor learning in the vestibulo-ocular reflex (VOR), suggesting that subtle disruption of P/Q Ca(2+) currents is sufficient to disrupt motor function. Basal VOR and optokinetic reflex performance were normal in the heterozygotes but severely impaired in the leaner and alpha1A knockout homozygotes.

    View details for DOI 10.1152/jn.00322.2006

    View details for Web of Science ID 000244090500031

    View details for PubMedID 17005620

  • Selective engagement of plasticity mechanisms for motor memory storage NEURON Boyden, E. S., Katoh, A., Pyle, J. L., Chatila, T. A., Tsien, R. W., Raymond, J. L. 2006; 51 (6): 823-834

    Abstract

    The number and diversity of plasticity mechanisms in the brain raises a central question: does a neural circuit store all memories by stereotyped application of the available plasticity mechanisms, or can subsets of these mechanisms be selectively engaged for specific memories? The uniform architecture of the cerebellum has inspired the idea that plasticity mechanisms like cerebellar long-term depression (LTD) contribute universally to memory storage. To test this idea, we investigated a set of closely related, cerebellum-dependent motor memories. In mutant mice lacking Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV), the maintenance of cerebellar LTD is abolished. Although memory for an increase in the gain of the vestibulo-ocular reflex (VOR) induced with high-frequency stimuli was impaired in these mice, memories for decreases in VOR gain and increases in gain induced with low-frequency stimuli were intact. Thus, a particular plasticity mechanism need not support all cerebellum-dependent memories, but can be engaged selectively according to the parameters of training.

    View details for DOI 10.1016/j.neuron.2006.08.026

    View details for Web of Science ID 000240997900019

    View details for PubMedID 16982426

  • Distinct patterns of stimulus generalization of increases and decreases in VOR gain JOURNAL OF NEUROPHYSIOLOGY Kimpo, R. R., Boyden, E. S., Katoh, A., Ke, M. C., Raymond, J. L. 2005; 94 (5): 3092-3100

    Abstract

    Motor learning must be capable of increasing or decreasing the amplitude of movements to meet the demands of the environment. One way to implement such opposite learned changes would be to store them with bidirectional plasticity mechanisms (i.e., long-term potentiation and depression at the same synapses). At the behavioral level, this scheme should result in similar patterns of stimulus generalization of increases and decreases in movement amplitude because the same synapses would be modified but in opposite directions. To test this idea, we quantitatively compared the stimulus generalization of learned increases and decreases in the gain (amplitude) of the vestibuloocular reflex (VOR) in mice and in monkeys. When examined across different sinusoidal frequencies of head rotation, decreases in VOR gain generalized more than increases in gain. This difference was apparent not only in the gain, but also the phase (timing) of the VOR. Furthermore, this difference held when animals were trained with high-frequency rotational stimuli, a manipulation that enhances frequency generalization. Our results suggest that increases and decreases in VOR gain are not exact inverses at the circuit level. At one or more sites, the plasticity mechanisms supporting decreases in VOR gain must be less synapse-specific, or affect neurons more broadly tuned for head rotation frequency, than the mechanisms supporting increases in gain.

    View details for DOI 10.1152/jn.00048.2005

    View details for Web of Science ID 000232528900011

    View details for PubMedID 16033945

  • Reversal of motor learning in the vestibulo-ocular reflex in the absence of visual input LEARNING & MEMORY Cohen, M. R., Meissner, G. W., Schafer, R. J., Raymond, J. L. 2004; 11 (5): 559-565

    Abstract

    Motor learning in the vestibulo-ocular reflex (VOR) and eyeblink conditioning use similar neural circuitry, and they may use similar cellular plasticity mechanisms. Classically conditioned eyeblink responses undergo extinction after prolonged exposure to the conditioned stimulus in the absence of the unconditioned stimulus. We investigated the possibility that a process similar to extinction may reverse learned changes in the VOR. We induced a learned alteration of the VOR response in rhesus monkeys using magnifying or miniaturizing goggles, which caused head movements to be accompanied by visual image motion. After learning, head movements in the absence of visual stimulation caused a loss of the learned eye movement response. When the learned gain was low, this reversal of learning occurred only when head movements were delivered, and not when the head was held stationary in the absence of visual input, suggesting that this reversal is mediated by an active, extinction-like process.

    View details for DOI 10.1101/lm.82304

    View details for Web of Science ID 000224178400012

    View details for PubMedID 15466309

  • Cerebellum-dependent learning: The role of multiple plasticity mechanisms ANNUAL REVIEW OF NEUROSCIENCE Boyden, E. S., Katoh, A., Raymond, J. L. 2004; 27: 581-609

    Abstract

    The cerebellum is an evolutionarily conserved structure critical for motor learning in vertebrates. The model that has influenced much of the work in the field for the past 30 years suggests that motor learning is mediated by a single plasticity mechanism in the cerebellum: long-term depression (LTD) of parallel fiber synapses onto Purkinje cells. However, recent studies of simple behaviors such as the vestibulo-ocular reflex (VOR) indicate that multiple plasticity mechanisms contribute to cerebellum-dependent learning. Multiple plasticity mechanisms may provide the flexibility required to store memories over different timescales, regulate the dynamics of movement, and allow bidirectional changes in movement amplitude. These plasticity mechanisms must act in combination with appropriate information-coding strategies to equip motor-learning systems with the ability to express learning in correct contexts. Studies of the patterns of generalization of motor learning in the VOR provide insight about the coding of information in neurons at sites of plasticity. These principles emerging from studies of the VOR are consistent with results concerning more complex behaviors and thus may reflect general principles of cerebellar function.

    View details for DOI 10.1146/annurev.neuro.27.070203.144238

    View details for Web of Science ID 000223246300021

    View details for PubMedID 15217344

  • Active reversal of motor memories reveals rules governing memory encoding NEURON Boyden, E. S., Raymond, J. L. 2003; 39 (6): 1031-1042

    Abstract

    Learning systems must be able to store memories reliably, yet be able to modify them when new learning is required. At the mechanistic level, new learning may either reverse the cellular events mediating the storage of old memories or mask the old memories with additional cellular changes that preserve the old cellular events in a latent form. Behavioral evidence about whether reversal or masking occurs in a particular circuit can constrain the cellular mechanisms used to store memories. Here we examine these constraints for a simple cerebellum-dependent learning task, motor learning in the vestibulo-ocular reflex (VOR). Learning can change the amplitude of the VOR in two opposite directions. Contrary to previous models about memory encoding by the cerebellum, our results indicate that these behavioral changes are implemented by different plasticity mechanisms, which reverse each other with unequal efficacy.

    View details for Web of Science ID 000185296100015

    View details for PubMedID 12971901

  • Contribution of background and target motion to the induction of motor learning in the interneurons VOR CREBELLUM: RECENT DEVELOPMENTS IN CEREBELLAR RESEARCH Ke, M. C., Raymond, J. L. 2002; 978: 525-525
  • Learning in the oculomotor system: from molecules to behavior CURRENT OPINION IN NEUROBIOLOGY Raymond, J. L. 1998; 8 (6): 770-776

    Abstract

    A combination of system-level and cellular-molecular approaches is moving studies of oculomotor learning rapidly toward the goal of linking synaptic plasticity at specific sites in oculomotor circuits with changes in the signal-processing functions of those circuits, and, ultimately, with changes in eye movement behavior. Recent studies of saccadic adaptation illustrate how careful behavioral analysis can provide constraints on the neural loci of plasticity. Studies of vestibulo-ocular adaptation are beginning to examine the molecular pathways contributing to this form of cerebellum-dependent learning.

    View details for Web of Science ID 000077737200013

    View details for PubMedID 9914237

  • Neural learning rules for the vestibulo-ocular reflex JOURNAL OF NEUROSCIENCE Raymond, J. L., Lisberger, S. G. 1998; 18 (21): 9112-9129

    Abstract

    Mechanisms for the induction of motor learning in the vestibulo-ocular reflex (VOR) were evaluated by recording the patterns of neural activity elicited in the cerebellum by a range of stimuli that induce learning. Patterns of climbing-fiber, vestibular, and Purkinje cell simple-spike signals were examined during sinusoidal head movement paired with visual image movement at stimulus frequencies from 0.5 to 10 Hz. A comparison of simple-spike and vestibular signals contained the information required to guide learning only at low stimulus frequencies, and a comparison of climbing-fiber and simple-spike signals contained the information required to guide learning only at high stimulus frequencies. Learning could be guided by comparison of climbing-fiber and vestibular signals at all stimulus frequencies tested, but only if climbing fiber responses were compared with the vestibular signals present 100 msec earlier. Computational analysis demonstrated that this conclusion is valid even if there is a broad range of vestibular signals at the site of plasticity. Simulations also indicated that the comparison of vestibular and climbing-fiber signals across the 100 msec delay must be implemented by a subcellular "eligibility" trace rather than by neural circuits that delay the vestibular inputs to the site of plasticity. The results suggest two alternative accounts of learning in the VOR. Either there are multiple mechanisms of learning that use different combinations of neural signals to drive plasticity, or there is a single mechanism tuned to climbing-fiber activity that follows activity in vestibular pathways by approximately 100 msec.

    View details for Web of Science ID 000076616600052

    View details for PubMedID 9787014

  • Multiple subclasses of Purkinje cells in the primate floccular complex provide similar signals to guide learning in the vestibulo-ocular reflex LEARNING & MEMORY Raymond, J. L., Lisberger, S. G. 1997; 3 (6): 503-518

    Abstract

    The neural "learning rules" governing the induction of plasticity in the cerebellum were analyzed by recording the patterns of neural activity in awake, behaving animals during stimuli that induce a form of cerebellum-dependent learning. We recorded the simple- and complex-spike responses of a broad sample of Purkinje cells in the floccular complex during a number of stimulus conditions that induce motor learning in the vestibulo-ocular reflex (VOR). Each subclass of Purkinje cells carried essentially the same information about required changes in the gain of the VOR. The correlation of simple-spike activity in Purkinje cells with activity in vestibular pathways could guide learning during low-frequency but not high-frequency stimuli. Climbing fiber activity could guide learning during all stimuli tested but only if compared with the activity present approximately 100 msec earlier in either vestibular pathways or Purkinje cells.

    View details for Web of Science ID A1997XF15800005

    View details for PubMedID 11536919

  • Behavioral analysis of signals that guide learned changes in the amplitude and dynamics of the vestibulo-ocular reflex JOURNAL OF NEUROSCIENCE Raymond, J. L., Lisberger, S. G. 1996; 16 (23): 7791-7802

    Abstract

    We characterized the dependence of motor learning in the monkey vestibulo-ocular reflex (VOR) on the duration, frequency, and relative timing of the visual and vestibular stimuli used to induce learning. The amplitude of the VOR was decreased or increased through training with paired head and visual stimulus motion in the same or opposite directions, respectively. For training stimuli that consisted of simultaneous pulses of head and target velocity 80-1000 msec in duration, brief stimuli caused small changes in the amplitude of the VOR, whereas long stimuli caused larger changes in amplitude as well as changes in the dynamics of the reflex. When the relative timing of the visual and vestibular stimuli was varied, brief image motion paired with the beginning of a longer vestibular stimulus caused changes in the amplitude of the reflex alone, but the same image motion paired with a later time in the vestibular stimulus caused changes in the dynamics as well as the amplitude of the VOR. For training stimuli that consisted of sinusoidal head and visual stimulus motion, low-frequency training stimuli induced frequency-selective changes in the VOR, as reported previously, whereas high-frequency training stimuli induced changes in the amplitude of the VOR that were more similar across test frequency. The results suggest that there are at least two distinguishable components of motor learning in the VOR. One component is induced by short-duration or high-frequency stimuli and involves changes in only the amplitude of the reflex. A second component is induced by long-duration or low-frequency stimuli and involves changes in the amplitude and dynamics of the VOR.

    View details for Web of Science ID A1996VY43300040

    View details for PubMedID 8922435

  • The cerebellum: A neuronal learning machine? SCIENCE Raymond, J. L., Lisberger, S. G., Mauk, M. D. 1996; 272 (5265): 1126-1131

    Abstract

    Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

    View details for Web of Science ID A1996UM88900038

    View details for PubMedID 8638157

Conference Proceedings


  • Hypotheses about the neural trigger for plasticity in the circuit for the vestibulo-ocular reflex Raymond, J. L., Lisberger, S. G. ELSEVIER SCIENCE BV. 2000: 235-246

    View details for Web of Science ID 000180918700017

    View details for PubMedID 10943129

  • Neural recordings and behavioral observations in the monkey vestibule-ocular reflex constrain the cellular mechanisms for cerebellum-dependent behavioral learning Lisberger, S. G., Raymond, J. L. EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER. 1996: 381-382

    Abstract

    Recordings from the cerebellum under behavioral conditions that cause learning in the vestibulo-ocular reflex (VOR) constrain the cellular mechanisms that could mediate learning. Analysis of the complex-spike responses of Purkinje cells demonstrates a mismatch between the properties of cerebellar long-term depression (LTD) in vitro and the signals available to guide learning in vivo. To resolve this mismatch, it may be necessary to assume that there are multiple cellular mechanisms of VOR learning, including both depression and potentiation.

    View details for Web of Science ID A1996WQ67500024

    View details for PubMedID 9089517

  • Error signals in horizontal gaze velocity Purkinje cells under stimulus conditions that cause learning in the VOR Raymond, J. L., Lisberger, S. G. NEW YORK ACAD SCIENCES. 1996: 686-689

    View details for Web of Science ID A1996BF92G00073

    View details for PubMedID 8694477

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