Project Summary Hearing loss is one of the most common problems associated with normal aging. Sensorineural hearing loss, caused by damage or loss of inner and outer hair cells and characterized by raised hearing thresholds in older subjects, is well known and can be diagnosed through audiograms or otoacoustic emissions (OAEs). However, there is a subtype of hearing loss known as central or “hidden” hearing loss that similarly affects aged individuals. Hidden hearing loss is so termed because those afflicted present with hearing deficiencies, but have normal audiograms; their hearing problems are therefore “hidden” from normal diagnostic measures. Although subjects with hidden hearing loss have normal hearing sensitivity, they struggle to detect and understand sounds presented above a background noise, and struggle with localizing sounds in space. The underlying cause of hidden hearing loss is not currently well known, but because of the common symptoms of decreased sound localization abilities with spared hearing thresholds, it is thought in part to arise from dysfunction in the auditory brainstem. We hypothesize that hidden hearing loss in aging subjects is a result of dysfunction in the auditory brainstem, specifically a mistiming of the inhibition arising from the medial nucleus of the trapezoid body (MNTB). To test this hypothesis, we will perform auditory measurements in Mongolian Gerbils, an animal model commonly used in binaural hearing research because of its hearing range similar to humans and their ability to utilize interaural time differences (ITDs) and interaural level differences (ILDs) as humans do. We will perform auditory measurements such as OAEs, audiograms, and monoaural and binaural auditory brainstem responses (ABRs) and envelope following response (EFRs) to assess both the peripheral hearing and binaural processing abilities of young and aged gerbils. We will also perform behavior tasks to determine the spatial hearing abilities of these cohorts and correlate changes in behavior with potential biomarkers of spatial hearing from our ABR results. Additionally, we will investigate if age-related dysfunction arises from age-related changes directly to the auditory brainstem, a reduction of input from peripheral areas of the auditory pathway, or both. To assess this, we will perform in vivo recordings from auditory brainstem nuclei to directly measure the firing properties of neurons from the MNTB. We will also examine levels of cochlear synaptopathy, a reduction in the synapses in the cochlea to the auditory nerve, in young and aging animals as a metric of peripheral hearing ability. We expect to see a decrease of temporal fidelity of inhibitory neurons from the MNTB in aging animals, which would correlate with an increase of cochlear synaptopathy, a reduction of ABR waveforms confirming synaptopathy, and a decrease of spatial hearing performance in these animals. Taken together, our electrophysiological, immunohistochemical a...