Behavioral and physiological measurements of hearing in mouse models of Alzheimer's Disease

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Project Summary Although Alzheimer’s disease and related dementias (ADRD) and hearing loss often co-occur, the nature of this relationship is still largely unknown. Many mouse models have been developed to better understand the physiological and behavioral effects of specific ADRD-related brain pathologies, but the research on hearing in these mice lags human studies and has not produced definitive results, with huge variability across laboratories. One study suggested that exposure to damaging noise may exacerbate the ADRD pathology in one ADRD model mouse strain, but other labs have not found similar effects in other mouse strains. Further, most researchers pursuing information about hearing, hearing loss, and aging in mouse models of ADRD utilize physiological methods in anesthetized mice or reflexive methods to assess hearing status. While these techniques are informative, neither method accurately portrays how an awake, behaving organism perceives the world around them. This is critical because epidemiological and audiological studies of humans with ADRD, as well as healthy-aging humans, rely primarily on behavioral measures of hearing dysfunction. For this reason, hearing in quiet and in noise at several time points in the mouse lifespan in three mouse models of ADRD using behavioral psychoacoustic assessments and physiological evoked potential techniques will be conducted. Comparisons of results from male and female mice trained with operant conditioning and positive reinforcement to those from anesthetized and unanesthetized mice using auditory brainstem response and middle latency response recordings will be made. Comparisons of behavioral results to physiological measurements will provide information about whether behavioral performance reflects central compensation processes and which physiological test conditions correspond to behavioral deficits. These experiments will help to better appreciate how aging, sex, and noise affect communication in mice, possibly leading to advances in understanding communication issues in human patients suffering from ADRD.