Sex difference in the efferent inner hair cell synapses of the aging murine cochlea

Efferent innervation of the inner hair cells changes over time. At an early age in mice, inner hair cells receive efferent feedback, which helps fine-tune tonotopic maps in the brainstem. In adulthood, inner hair cell efferent innervation wanes but increases again in older animals. It is not clear, however, whether age-related inner hair cell efferents increase along the entire range of the cochlear frequencies, or if this increase is restricted to a particular frequency-region, and whether this phenomenon occurs in both sexes. Age-related hearing loss, presbycusis, affects men and women differently. In mice, this difference is also strain specific. In aging black six mice, the auditory brainstem response thresholds increase in females earlier than in males. Here, we study age-related increase of the inner hair cell efferent innervation throughout the cochlea before hearing onset, in one month old and in ten months old and older male and female black six mice. We collected confocal images of immunostained inner hair cell efferents and quantified the labeled terminals in the entire cochlea using a machine learning algorithm. The overall number of the inner hair cell efferents in both sexes did not change significantly between age-groups. The distribution of the inner hair cell efferent innervation did not differ across frequencies in the cochlea. However, in females, inner hair cells received on average up to four times more efferent innervation than in males per each of the frequency regions tested. Sex differences were also found in the oldest age-group tested (≥ 10 months) where on average inner hair cells received six times more efferents in females than in males of matching age. Our findings emphasize the importance of including both sexes in sensorineural hearing loss research.