This project is guided by the hypothesis that the aging auditory system loses its ability to process acoustic transients efficiently, so that elderly listeners are unable to perceive rapidly modulated speech sounds in complex acoustic environments. This deficits yields minor problems in quiet for the human listener, but causes serious problems in naturalistic settings with competing uncertain signals. The goal of this project is to describe and understand this effect of acoustic complexity in animal models, consisting of aging CBA/CaJ and C57BL/6J mice, and young KCNA1 and KCNA3 potassium-channel knockout mice. Behavioral experiments in mice parallel those in human psychophysics (Project 1) as well as physiological and anatomical studies in mice (Projects 3 and 4), in similar acoustic settings. We will test the hypothesis that temporal, spectral, and spatial acuity in old mice will suffer in the presence of multiple sound sources, as human listening does in complex surroundings. We hypothesize that KO mice will respond to non-synchronous inputs (KCNA1) but fail to track fast repetitive inputs (KCNA3), and we will test the hypothesis that young KO mice, old normal mice and old human listeners share similar problems. These experiments with KO mice are coordinated with Projects 3 and 4 in order to understand the molecular bases of these deficits, and to examine the hypothesis that the aged mouse, and by extension, the aged human listener has an altered expression of these ion channels. We will examine the effects of neurochemical intervention (increases and decreases in 5HT, GABA, and ACH) on temporal, spectral, and spatial acute to parallel studies in electrophysiology, testing hypotheses generated by data showing neurotransmitter changes in old rodents. In addition to extending our understanding of age effects on hearing, these identify acoustic variables and physiological processes most sensitive to age-related deficits. This work is intended to identify targets for intervention strategies and to provide direction for studying the genetic substrates of presbycusis. Note: Project 1= Binaural and Spatial/Temporal Hearing and Audiology (Frisina); Project 3= Animal Single Unit and Evoked Potentials Neurophysiology (Walton); Project 4= Animal Neuroanatomy, Emissions, and Cellular Neurobiology (Frisina).
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