This research proposal examines the impact of acoustic trauma, development and aging on the innervation of cochlear hair cells, with particular focus on the role of the efferent system. Emerging evidence suggests that afferent and efferent synapses interact in undefined ways during a developmental critical period, and in parallel with altered acoustic function. How might such interactions occur? Does activity of the hair cell determine synaptic arrangements, or do synapses ?compete? for territory? In particular, do efferent inputs play an instructive role in the differentiation of hair cell function? Or, are efferent (and afferent) synapses dependent upon changes in hair cell excitation? To approach these questions, hair cell excitability and synaptic function will be detailed before and after acoustic trauma in AChR-null (?9 null) mice, and in those with gain of function AChRs (?9L9?T). Auditory function and synaptopathy will be assessed in aging animals in ?9 null and ?9L9?T mice. Finally, the developmental maturation of synapses on IHCs will be examined in TMC2 mechanotransduction null mice.
. The cochlea receives efferent feedback from the brain. These cholinergic synapses inhibit cochlear hair cells and are rearranged during development and after hearing loss. This proposal aims to explore the determinants of those rearrangements.
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