This program explores the mechanisms that underlie the perception of complex sounds. Broad in its scope, its unifying theme is the problem of auditory processing in noise. There are three principal issues: 1) Spatial hearing in ambient noise. 2) Descending modulation of sound perception, considered from the level of efferent regulation of electromotility in the cochlea to animal behavior. 3) Stimulus-provoked cell death and protection of auditory structure and function by regenerative processes in the cochlea. The program is built on testable hypotheses and state-of-the-art methodology and is motivated by clear clinical insights. Six individual projects are based in the areas of cortical physiology, animal behavior, cochlear physiology, neuropharmacology, molecular genetics, and cochlear mechanics. The projects relate directly to deafness and to the treatment of deafness by investigating mechanisms of noise- induced acoustic trauma, novel approaches to evaluation of cochlear function, and feasibility of gene transfer in the cochlea. The proposed interdisciplinary approach and mutual interaction among the six projects is enhanced by three core resources. The morphology core provides for the necessary preparation and analysis of tissue from each of the six projects. The technical core will construct and maintain unique electrical and mechanical system components required by the individual projects. The administrative core supports all projects and cores. Although meritorious on their own, the six projects and three cores, taken as a whole, constitute a unique and integrated scientific endeavor. In summary, this program will provide significant new understanding of cortical mechanisms of complex signal processing, the processes underlying temporary and permanent hearing loss, the excitotoxic damage of cochlear nerve fibers, and a genetic therapy to rescue those damaged cells.
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