The aged human has difficulty in detecting and identifying complex acoustic signals, particularly in noise. These impairments result in part because the signal is less audible (attenuation), in part because the clarity of audible signals is diminished (distortion). Attenuation is assumed to result from cochlear degeneration. The causes of distortion are more controversial: our hypothesis is that it results from a combination of peripheral loss and central degeneration due to aging. Age-related changes in the processing of complex sounds have not been studied in animals, and therefore controlled experimental laboratory investigations of the development of hearing impairment with age, its environmental and physiological antecedents, and its consequences for auditory processing have not been possible. In this project aged humans and three animal models of presbycusis will be studied, the C57BI/6J and the CBA/J murine strains, and the Fischer 344 rat, with male and female subjects represented in each population. Behavioral testing of humans will examine presbycusis with an objective behavioral method, compare the impairment for simple and complex acoustic stimuli, and provide the criterial targets for establishing the validity of cross-species extrapolations: testing will be done in young adults and in >60 year olds. The C57BI mouse is the model for an early onset peripheral loss, as it shows a progressive loss, as it shows a progressive loss in high-frequency bearing, which spreads to lower frequencies, similar to the human, but beginning within the first 6 months of life: testing will take place at 1-2 and 6-8 months of age. The CBA is a model for a predominantly central aging loss, as it shows a peripheral loss late in life, like the human, but the loss is relatively mild: testing will take place at 1-2, 6-8, and >22 months of age. The Fischer 344 rat is a second model of a predominantly central aging loss, and is used to be sure that findings from the CBA mouse are not specific to its possible idiosyncratic genetic makeup: testing will take place at 1-2 and >22 months of age. The Fischer 344 shows central changes in neurotransmitter systems that have been shown to occur in aging humans, and which, when simulated in young humans and in young rats, produce a deficit in the detection of acoustic transients similar to that seen in the aged, with no loss of apparent audibility for simple signals. Thus these three models are chosen to represent different aspects of the loss of auditory function in aged humans. Measures of audibility, startle reflex vigor, temporal acuity, frequency resolution, and critical band-width will provide tests of the hypotheses that an age-related loss in complex signal processing is a primary deficit, or otherwise, that it is secondary to changes in audibility, and that this loss is in central auditory pathways, or otherwise, occurs at the periphery. Groups of rodents with characterized age-related deficiencies in hearing will be made available to Projects 3 and 4 for subsequent electrophysiological and anatomical investigations.
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