Cochlear neuron functions and diseases

About This Grant

Previous research has demonstrated that the precise sensitivity, frequency selectivity, and sound tuning in cochlear amplification rely partly on hair cell (HC), hair bundle motility, and the somatic electromotility of outer hair cells (OHCs). The OHCs account for ~75% of the sensory HCs; the remaining 25% consists of inner HCs (IHCs), the canonical afferent receptors. The fewer IHCs’ activity is transmitted through about 95% of the auditory (type I) afferent neurons, whereas the ample OHCs’ activity is transmitted by ~ 5% of auditory (type II) afferent neurons to the brain for integration and perception. Type II neurons are characterized by small unmyelinated cell bodies with extensive neurite arbors that receive inputs from multiple OHCs, making studying their broad receptive field and normal physiology quite challenging. Nevertheless, we have developed precise methods to assess type II auditory neuron functions. Our studies have led to the hypothesis that specific functional and molecular markers can be used to identify type II neurons and that they represent a functionally diverse neuronal population based on their cochlear frequency map assignment. Our plan utilizes innovative molecular biology, biochemical analyses, electrophysiology, and imaging techniques in gene-targeted and optogenetic mouse models to determine type II neuron-OHC physiology. Our first objective is to identify type II neurons' molecular, proteomic, and functional markers and examine their functional roles using genetic tools. In our second objective, we will determine their in vivo and in vitro functions. Finally, our third objective is identifying the mechanisms underlying the encoding features of type II neuronal transmission of OHC activity. Through these studies, we aim to uncover crucial features of type II auditory afferent neurons that innervate OHCs. This will provide a comprehensive understanding of afferent auditory neurons, essential for treating sensorineural hearing loss (SNHL).