Mechanisms of Auditory Circuit Development

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PROJECT SUMMARY The long-term goal of my laboratory is to elucidate the mechanisms that regulate auditory perception, and how defects in hair cells and auditory neurons cause disease. We propose here to study the mechanisms that regulate the differentiation, connectivity and function of spiral ganglion neurons (SGNs). Our central hypothesis is that SGNs are a diverse group of neurons with different connectivity patterns and functions, and that diversification of SGNs and their connectivity depends on signals provided by hair cells. To test our hypothesis, we will combine studies in genetically modified mice with histology, imaging, genomics, electrophysiological and hearing tests to study SGN connectivity and function. We will map SGN projection patterns, define how mutations linked to deafness affect SGN differentiation and projection patterns, and use genetic manipulations combined with electrophysiology and genomic tools to identify signals initiated by hair cells that affect SGN differentiation. Our preliminary data show the feasibility of our approach, demonstrating that SGNs are a molecularly diverse group of neurons with different projection patterns and that defect in hair cells affect SGN differentiation. We anticipate that our findings will define mechanisms by which hair cells affect SGNs to regulate their diversification into subtypes with different functions and connectivity patterns.