The ribbon synapse in inner hair cells of the adult mouse cochlea. (360G-Wellcome-093084_Z_10_Z)

This project addresses the cellular mechanisms of synaptic transmission of information from adult sensory inner hair cells related to the dynamic range problem . It will use mouse models, but focussing on adult hair cells. JFA has recently developed a method for making whole cell recording relatively easily from adult cells and imaging their ribbon synapses, by leaving the cells in situ, in the temporal bone. There is no upper age limit to the cells which can be studied and so removes the tec hnical issues of extrapolating from early stage data, bridging the gap to ages where nerve fibre recordings are made. The project is designed to resolve cellular mechanisms of sound level segmentation that occurs between different subpopulations of fibres. Fast multiphoton laser scanning microscopy will be used to quantify a gradient of calcium and vesicle dynamics at multiple ribbon sites in the basal pole. The structural basis of this (planar) cell polarity will be studied in wild type and in mutant mice with PCP abnormalities and with ribbon synapse protein mutations. Mouse models of hearing loss will be used to obtain insights into age-related neural changes and to provide a deeper understanding of some audiological measures of presbyacusis.