PROJECT SUMMARY/ABSTRACT Individuals with sensorineural hearing loss often have impaired ability to localize audible sound sources, but the physiological reason for this impairment is unknown. This project involves experiments to test whether rabbits— a species with a frequency hearing range similar to that of humans—also exhibit hearing-loss-related deficits in sound localization, and whether hearing loss degrades the transmission of information about sound source location by neurons in the central nucleus of the inferior colliculus—the first brain area along the mammalian central auditory pathway where information about sound source location converges. Hearing loss will be induced in anesthetized rabbits via noise overexposure and quantified via changes in auditory brainstem response (ABR) thresholds and binaural interaction component amplitudes. Rabbits will be trained to perform a behavioral sound localization task using operant conditioning techniques. Behavioral localization performance will be compared before and after noise overexposure to determine whether rabbits exhibit a hearing-loss-related deficit similar to humans. Single-unit data will be collected from the inferior colliculi of a separate cohort of rabbits in response to acoustic stimuli to measure neuronal sensitivity to sound source location or specific sound localization cues, including interaural time difference and interaural level difference cues. Neuronal sensitivity to sound source location or sound localization cues will be compared between normal-hearing and hearing-impaired rabbits to determine whether noise-induced hearing loss degrades the transmission of information related to sound localization in the inferior colliculus. Neuronal and behavioral data will be compared to each other using a neural population decoder of sound-source location to determine whether potential hearing-loss-related deficits in behavior are consistent with deficits in neural function at the level of the inferior colliculus. Behavioral and neural experiments in Aim 1 will be performed on rabbits with a mild degree of hearing loss (~25-dB ABR threshold shifts) that leaves most cochlear hair cells alive, whereas behavioral and neural experiments in Aim 2 will be performed on rabbits with a moderate degree of hearing loss (~60-dB ABR threshold shifts) that preferentially kills outer hair cells while leaving most inner hair cells intact. Hair cell counts and counts of synapses between inner hair cells and auditory nerve fibers will be verified at the end of behavioral or neural data collection via confocal immunofluorescence microscopy. Together, the two aims will determine whether noise overexposure alters localization behavior and/or binaural coding in the inferior colliculus of rabbits, and whether such changes depend upon the survival of outer hair cells.