Anthony Peng, PhD, University of Colorado Denver

Our sense of hearing relies on converting sound vibrations into electrical signals in sensory hair cells. The apically located stereocilia hair bundle is responsible for this conversion of energy through the mechanotransduction process. The regulation of the sensitivity of the mechanotransduction process likely contributes to maximizing the dynamic range of hearing and contributes to the function of the cochlear amplifier. At least two mechanisms can regulate the sensitivity of mechanotransduction. cAMP has been shown to reduced sensitivity of the channel, and we recently described the mechanical changes in the hair bundle leading to the reduction in sensitivity. A second mechanism for sensitivity control is slow adaptation. We recently challenged the prevailing model of slow adaptation and proposed a new model of how slow adaptation functions.

Radha Kalluri, PhD, University of Southern California

The cell bodies of vestibular and auditory ganglion neurons express a diverse range of ion channels and neurotransmitter receptors. This diversity provides a rich biophysical substrate for shaping the excitability of neurons and expands the populations’ repertoire for sensory signaling. In the vestibular nerve, the temporal precision needed to code rapid head movements is determined by neurons firing at irregular intervals whereas the ability to sensitively detect slow head movements is determined by neurons firing at regular intervals. I will describe recent work from my laboratory testing the idea that ion channels resident in the membranes of vestibular neurons are responsible for producing this diversity in spike-timing regularity. Our results suggest that definitive relationships between ion channel composition and neuronal function cannot be established without also considering the impact that efferent modulation has on individual ion channels. I’ll show that the role played by an ion channel can be context dependent; varying based on its density, and activation state, as well as on its interactions with other channels. I will end the talk by describing our recent work linking the ion channel properties of spiral ganglion neurons to sub-groups of Type I auditory afferents. 

Ruth Litovsky, PhD, University of Wisconsin

Our lab studies children and adults who receive bilateral cochlear implants (BiCI), or adults with single-sided deafness receiving a CI in the deaf ear (SSD-CI). Bilateral hearing typically improves localization of sounds and segregation of speech from background noise compared with unilateral hearing. However, patients typically perform worse than normal hearing listeners. We use several approaches to understand mechanisms driving gaps in performance, including asymmetry in sensitivity to monaural information such as modulation detection. Further interaural mismatch in place of stimulation along the cochlea, age at onset of deafness and age at implantation contribute to recovery of binaural hearing. Because CI processors do not preserve binaural cues with fidelity, we use research processors to generate multi-channel binaural stimulation strategies that introduce different rates of stimulation across the electrode arrays, thereby preserving rates that are important for both binaural sensitivity and speech understanding. In addition, eye gaze studies reveal developmental factors that in decision-making that are not observed with measures of threshold. Finally, pupillometry studies provide insight into the impact of integrating inputs from two ears, whereby in some instances improved performance with two ears can be “costly” in the listening effort domain.

Sean Megason, PhD, Harvard University

The Megason lab uses timelapse confocal microscopy of developing zebrafish embryos to capture complete cell level views of how organs are built. Combined with image analysis, modeling, and molecular perturbations we uncover the mechanisms that allow cells to coordinate their activities to create exquisite structures like the inner ear.

Pim van Dijk, PhD University of Groningen

Hearing loss is the most important risk factor for tinnitus. Hearing loss is associated with changes in the functional organization of the central auditory system. Animal studies show that this includes changes in spontaneous neural activity after the induction of hearing loss. In this talk, I will present data showing that hearing loss in humans is associated with changes in functional organization of the auditory cortex. Remarkably, in the subjects with tinnitus in addition to hearing loss, these changes seem to be less pronounced. These data suggest that tinnitus is associated with incomplete central adaptation to hearing loss. Future therapies for tinnitus may need to focus normalizing central adaption to hearing loss.

Ulrich Mueller, PhD, Johns Hopkins

Organisms of all phyla express mechanosensitive ion channels with a wide range of physiological functions. In recent years, several classes of mechanically gated ion channels have been identified. Some of these ion channels are intrinsically mechanosensitive. Others depend on accessory proteins to regulate their response to mechanical force. The mechanotransduction machinery of cochlear hair cells provides a particularly striking example of a complex force-sensing machine. This molecular ensemble is embedded into a specialized cellular compartment that is crucial for its function. Notably, mechanotransduction channels of cochlear hair cells are not only critical for auditory perception. They also shape their cellular environment and regulate the development of auditory circuitry. Here we summarize recent discoveries that have shed light on the composition of the mechanotransduction machinery of cochlear hair cells and how this machinery contributes to the development and function of the auditory system.

Basile Tarchini, PhD, The Jackson Laboratory

Fundamental to interacting with our surroundings, hearing and balance require sensory 'hair’ cells in the inner ear to transduce a mechanical signal (sound, body position, head movements) into electrical impulses relayed to the brain. Research in our laboratory aims to understand how hair cells acquire, organize and maintain their mechanically sensitive compartment, the stereocilia bundle. We are particularly interested in elucidating the essential contribution made by guanine nucleotide-binding (G) proteins. In recent years, we identified multiple regulators of inhibitory G proteins (Gai, or GNAI) required for auditory and balance function. Our work suggests that Gai proteins assume distinct roles to both polarize the morphogenesis of the stereocilia bundle and instruct hair cell orientation in all sensory organs. A molecular understanding of stereocilia bundle development and maintenance is key to explaining hearing loss and balance disorders, and it empowers emerging therapies to rescue or regenerate hair cells that are terminally differentiated in mammals.