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bioRxiv · 10.64898/2025.12.27.696605

Age-Related Changes to Olivocochlear Efferent Neurons in Mice with Pathological Hearing

Suthakar, K.·Douglas-Kinniburgh, H.·Ryugo, D. K.
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Abstract

One of the fundamental features of age-related hearing loss (ARHL) is difficulty discriminating speech signals from background noise. In addition to protecting the ear from acoustic trauma, olivocochlear (OC) efferent neurons participate in signal discrimination by virtue of their inhibitory actions on auditory nerve firing. Given the time course of peripheral degeneration in ARHL, we sought to investigate the central degeneration of medial (MOC) and lateral (LOC) efferent neurons in mutant mice that exhibit genetic hearing loss or deafness at different ages. Tests of cochlear function were combined with anatomical and morphological quantification of changes to somatic number, morphology, and location of OC neurons. Neuronal tract tracing methods were employed to label OC neurons in 1-, 3-, and 6-month-old CBA/CaH mice with normal hearing; DBA/2J mice with progressive, high frequency hearing loss; and homozygous Shaker2 mice with congenital deafness. Deaf Shaker2-/- animals exhibited age-related atrophy and loss of MOCs, with contralateral MOCs more affected than ipsilateral MOCs, while LOCs were largely unaffected. No such OC degeneration was observed in DBA/2J mice, even after progressive elevation of low frequency auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE) thresholds. Thus, OC efferent neurons can appear morphologically normal in the complete absence of acoustic input in early life (as in deaf Shaker2-/- animals) and that the retention of these neurons is not affected by late onset high-frequency hearing loss observed in DBA/2J animals. Differential patterns of MOC neuron degeneration may affect functional plasticity of auditory brainstem feedback circuitry in ARHL.

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Suthakar, K., Douglas-Kinniburgh, H., Ryugo, D. K.. 2025-12-29. Age-Related Changes to Olivocochlear Efferent Neurons in Mice with Pathological Hearing. https://doi.org/10.64898/2025.12.27.696605

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