The decline of auditory discrimination abilities is a common and troublesome companion of aging that interferes with the perception of speech and other important sounds. This problem is often associated with age-related loss of hearing sensitivity (presbycusis), but can also occur in the absence of significant threshold elevations. In either case, a breakdown of normal neural coding processes in the auditory central nervous system must often play an important part in the loss of discrimination ability. The proposed research project will investigate this problem by studying neural coding using two inbred mouse strains a models: the C57BL/6J strain, which shows substantial presbycusic loss, and the CBA/J strain, which shows little sensitivity loss with age. Neurophysiological experiments will be performed on mice in several age-ranges, obtaining extracellular neuronal recordings from the ventral cochlear nucleus and central nucleus of the inferior colliculus. Age-related changes in neuronal response parameters thought to be involved in the coding of frequency and intensity of sounds will be described in detail. The representation of frequency in the brain (tuning curves; tonotopic organization), which has recently been shown to change in aging mice, will be thoroughly studied with physiological and anatomical methods. Perceptual/behavioral correlates of age-related changes in neural function and organization will be otained to help determine the significance of the latter. The state of the peripheral auditory system will be evaluated electrophysiologically and histologically to aid in interpreting all of the above experiments. The overall project will employ these methods in two closely related phases. Phase 1 will describe the normal aging process in the two strains. Phase 2 will utilize experimentally induced hearing loss in order to tease apart the roles of age, peripheral hearing loss, genotype, and their interactions in contributing to the observations of Phase 1. Finally, the feasibility of ultimately applying certain findings to humans afflicted with presbycusis will be assessed.
