Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure

The early onset of peripheral deafness significantly disrupts the proper development of the auditory system. Likewise, exposure to loud noise during early development produces a similar disruptive effect. Before hearing onset in altricial mammals, cochlear inner hair cells exhibit spontaneous electrical activity that activates primary afferents and propagates into the central nervous system. This activity is crucial for auditory system maturation and is modulated by the medial olivocochlear efferent (MOC) feedback via α9α10 nicotinic cholinergic receptors present in inner hair cells. In adults, these receptors are restricted to outer hair cells, where they mediate feedback from the MOC system to regulate cochlear amplification. Although the MOC system’s protective role to prevent noise-induced hearing loss in adulthood is well-established, its influence during early developmental stages -especially in response to exposure to loud noise-remains largely unexplored. In this study, we examined the effect of the MOC system in the ears of sound-exposed mice during the early postnatal developmental period, by using genetically modified mice - α9 knockout and α9 knock-in models - with either absent or enhanced cholinergic activity. Our findings reveal that both increased and absent olivocochlear activity result in altered auditory sensitivity at the onset of hearing, along with long–range alterations in the number and morphology of ribbon synapses. Furthermore, exposure to loud noise during early development causes long-lasting damage in both wild-type and α9 knockout mice, which lack functional MOC feedback, with effects persisting into adulthood. In contrast, mice with enhanced cholinergic activity were protected from noise-induced damage, with no long-term effects on auditory function. These results highlight the increased susceptibility of the auditory system during early postnatal development. Moreover, they indicate that an enhanced MOC feedback shields the auditory system from noise damage during this period.