The role of ion channels in shaping the function of inner ear neurons

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SUMMARY The cell bodies of vestibular ganglion neurons express a diverse range of ion channels and neurotransmitter receptors. This diversity provides a rich biophysical substrate for shaping the intrinsic excitability of individual 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 detect slow head movements sensitively is determined by neurons firing at regular intervals. Here we test whether the ion channels resident in the membranes of vestibular neurons produce this important diversity or whether other specializations of dendritic and synaptic morphology are also needed. The resolution of this question requires joint characterizations of ion channel composition and dendritic morphology in individual neurons. To provide this, we will perform patch-clamp recordings combined with single-cell labeling in semi-intact neuro-epithelium preparations in which neurons are still connected to their hair cells. Definitive relationships between ion channel composition and neuronal function cannot be established without considering the impact of efferent modulation on individual ion channels. Using pharmacology, we will define the impact of cholinergic efferent signals on two ion channels identified as being prominent for controlling the firing patterns and excitability of vestibular ganglion neurons. We will test if some neurons are more receptive to this modulation than others. Identifying such differences may also reveal opportunities for selectively targeting therapeutics to specific neuron groups. We will combine the unique joint characterizations of ion channels and dendritic morphology from our experiments to create computational models to examine the relative importance of ion channel composition and dendritic integration on vestibular afferent responses. Overall, our work integrates powerful computational and experimental approaches to advance our understanding of a fundamental aspect of vestibular function.