Mechanical amplification by outer hair cells (OHCs) enables mammals to produce their high sensitivity and sharp frequency selectivity. The molecular motor that powers the OHC’s unique motile function is the protein Prestin. In order to perceive sound, the correct nerve innervation with hair cells must be established. Despite great efforts from the hearing research community, many questions regarding the development and maturation of neural innervation to hair cells remain unsolved. We have found that synapses in OHCs that lack prestin appear abnormal. This observation led us to suspect that OHCs might play an important role in establishing their own synapses. To test this hypothesis, we will investigate prestin’s role in synaptogenesis using several prestin transgenic mouse models that carry OHCs with modified electromotility. In AIM 1, we will examine nerve innervation consequences when OHC properties are changed using immunofluorescence methods. In AIM 2, we will explore the molecular mechanisms which underlie these changes by performing single cell RNA–sequencing. We will also explore the reciprocal interactions between hair cells and neurons by focusing on prestin, a unique OHC gene/protein that plays an essential role in OHC function. This proposal aims to look at OHC innervation from an entirely different perspective. Uncovering a novel role for prestin in synaptogenesis will not only allow us to gain a deeper understanding of the molecular mechanisms underlying cochlear amplification, but also provide essential knowledge needed to apply in new therapeutic strategies to re-establish primary connections from the sound transducers to the ascending auditory nerve pathways.
|Effective start/end date||1/1/16 → 12/31/17|
- American Hearing Research Foundation (Agreement 1/20/16)