Age-Related Changes to Auditory Temporal Processing in Mice with and without Age-Related Hearing Loss
Abstract
Most older adults experience age-related changes to their hearing, either in the form of hearing loss, or in a more subtle form of hearing impairment, causing difficulties understanding speech in acoustically challenging environments. As the population grows older, better solutions will be needed to alleviate age-related hearing deficits. To test new potential therapies for age-related changes to hearing, preclinical models must be identified and characterized. The studies included in this dissertation measure translationally relevant electrophysiological signals from mice at multiple ages, with and without severe hearing loss, to identify age-related changes to cortical activity, both at baseline and in response to acoustic stimuli. Acoustic stimuli were used to test various aspects of auditory processing, including amplitude modulated signal processing, which supports speech comprehension. We found that age-related changes in the responses to the acoustic stimuli selected for this study mirror many of the changes observed in older humans. We observed age-related deficits in responses to more challenging amplitude modulated signals, even in the absence of hearing loss. In mice with hearing loss, we observed evidence of central gain and disrupted temporal processing. Both results, which mirror age-related changes to human hearing, suggest that aging mice are a useful model for auditory processing in older humans. We then evaluated the therapeutic potential of nicotine for treating age-related changes to auditory temporal processing, with promising results. Nicotine appeared to improve temporal processing in old mice, partially reversing age-related, frequency-specific changes in event-related spectral perturbations and amplitude modulation following responses. This dissertation characterizes translationally relevant preclinical measures of age-related changes to auditory processing, with the aim of testing interventions and therapeutics, such as nicotine, for the treatment of age-related auditory temporal processing deficits.