The research in this proposal examines the effects of acoustic overstimulation at the ?top and bottom"""""""" of the hair cell, and at the """"""""output"""""""" from the hair cell. The top of the hair cell is where acoustic information is transduced via hair bundle movements and the gating of mechanosensitive transduction channels. Various machinery at the bottom of the cell culminates in the release of neurotransmitter. The net effect of these hair cell actions is the production of discharge activity in the cochlear nerve. Tools are now available to dissect the processes in each of these cellular compartments and examine their contribution to the loss and recovery of chick auditory function after exposure to damaging levels of sound. Whole-cell patch clamping of tall hair cells measures transduction currents during in vitro water-jet stimulation. Measures of membrane current and capacitance describe tall hair cell calcium currents and exocytotic processes. The profile shape of the tall hair cell stereocilia staircase, and tip-link morphology, are also evaluated. In vivo recordings of cochlear nerve activity gauge hair cell output. Tracer-dye labeling of cochlear nerves identifies tall hair cell location on the sensory surface. These methods are applied in control and sound damaged ears.
Aims are proposed that test hypotheses concerning the susceptibility to, and consequence of, acoustic overstimulation on the tall hair cell and cochlear nerve. The first two aims dissect the effects of overstimulation on the cellular mechanism of transduction and exocytosis. The remaining two compliment the in vitro investigations and explore related in vivo phenomena in cochlear nerve activity. The objective of the research is to develop an integrated picture of peripheral pathophysiology in the hair cell and cochlear nerve. The hypotheses examined are: 1. The tall hair cell transduction process is damaged by overstimulation, and tall hair cell susceptibility to damage is related to the profile shape of the sensory hair bundle; 2. Overstimulation disrupts calcium influx, the kinetics of exocytosis, and the size of the releasable pool of vesicles; 3. Neural adaptation in chick cochlear nerve units changes as a consequence of exposure to intense sound, and; 4. Cochlear nerve abnormal rate-intensity functions two-weeks post exposure originate from tall hair cells adjacent to the """"""""patch"""""""" lesion.
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