Ion Channel Function in Auditory & Vestibular Hair Cells

The long term goal of these projects is to characterize and identify the physiological and molecular basis of sensory signaling in the inner ear. Both auditory and vestibular organs contain mechanosensitive hair cells that initiate the sensory signal; modify, tune and amplify the signal; and then transmit the signal to the postsynaptic neurons of the eighth cranial nerve. Understanding how these sensory signals are generated, modified and relayed is necessary to provide a foundation for design of future treatments for inner ear dysfunction. The proposed studies focus on ion channel contributions to hair cell function and are organized around two specific aims. 1) We aim to develop a better understanding of a novel form hair cell mechanosensitivity that is present in auditory hair cells during development. We will characterize the response biophysically, pharmacologically and physiologically. We will localize the response, both the site of optimal stimulation and the site o transduction. We will characterize the genes and proteins required for the response and we will use genetic, viral and chemical inhibition to investigate its function. 2) To provide a more complete description of sensory adaptation in the mammalian inner ear, we will investigate the functional and molecular properties of adaptation in auditory and vestibular hair cells. Because these organs detect mechanical stimuli with very different temporal characteristics, we hypothesize that there may be significant biophysical and molecular differences between hair cells of auditory and vestibular organs. We will use pharmacological, chemical-genetic, viral-mediated gene knockdown and conditional genetic deletion of target genes to systematically investigate the properties of sensory adaptation in these hair cells. The data that emerge from the proposed studies will provide innovative and significant advances in our understanding of the development, generation and transmission of sensory information in the mammalian inner ear.