A series of experiments are proposed which investigate the functional consequence of either permanent inner hair cell (IHC) loss using carboplatin or temporary degeneration of eight nerve fibers using kainic acid. The experimental animal will be the chinchilla. Preliminary data from this laboratory demonstrate different patters of changes in evoke potential amplitude at varying locations in the auditory nervous system following injection of carboplatin or application of kainic acid to the round window. We will survey outer hair cell integrity by recording distortion product otoacoustic emissions from the early canal of each animal. Following baseline studies, we will evaluate the time course of the functional consequence of carboplatin and kainic acid on the responses from the eighth nerve, inferior colliculus and auditory cortex. Using this approach, we will investigate the role of IHC function on auditory function and will study functional reorganization in the auditory system in response to permanent IHC loss and transient deafferentation. Several experiments will use GABA blockers to test the hypothesis that disinhibition plays a role in compensatory changes seen in central auditory structures following peripheral damage. A fundamental assumption of this work is that a dissociation of peripheral and central effects of ototoxic insults, or a differing time course of recovery is evidence of compensatory functional reorganization.
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