2023-24 Sensory Neuroscience & Engineering Seminar Series
Towards Hearing Restoration: Investigating the Genetic Restrictions on Hair Cell Regeneration in the Mature Inner Ear
Melissa McGovern, PhD, University of Pittsburgh
One significant cause of hearing loss is the loss of sensory cells in the inner ear called hair cells. These cells detect sound from the environment and send signals to the brain. These hair cells are susceptible to numerous insults including loud noises (think rock concerts, military activities, industrial noise exposure), ototoxic medications (for example aminoglycoside antibiotics and platinum-based chemotherapeutics), and the natural aging process.
Melissa investigates the ability of the mature mouse ear to respond to genetic reprogramming of non-sensory cells. She has found that cells directly adjacent to the sensory hair cells (called supporting cells) are responsive to reprogramming following hair cell loss. These cells convert into hair cells and attract innervation; however, they do not yet transmit sound signals to the brain. In addition, Melissa has found that other cells within the hearing organ can robustly respond to genetic reprogramming and be converted into hair cells. While these cells are not in the correct location for hearing recovery, these are thought to be the cells that form a scar in the ear following severe cochlear damage. This makes them an important target for hearing restoration therapeutics.
Physics of the Auditory System
Dolores Bozovic, PhD, University of California Los Angeles
Hair cells of the auditory system constitute a remarkable biological sensor that exhibits nanometer-scale sensitivity of mechanical detection. Our experiments explore the active nonlinear processes behind the detection of very weak signals. We demonstrate the presence of chaos in the innate motility of active bundles, and explore both theoretically and experimentally its role in enhancing the sensitivity of detection. We further show that these cells utilize weakly chaotic dynamics to combine sensitive response with high temporal resolution. The presence of chaos in individual hair bundles also aids in the synchronization between coupled hair cells, and gives rise to new dynamical states. Finally, we explore the neural mechanisms that reduce and control the responsiveness of the cell. Specifically, we show that the efferent neurons serve as a gain control system, which can strongly affect the very compliance of the mechanosensory cells.
Mechanisms of Hair Cell Mechanotransduction Sensitivity Control
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.
Biophysical diversity amongst inner ear bipolar neurons
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.
Impact of auditory deprivation and plasticity on binaural hearing in cochlear implant users
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.