Early Noise Exposure and Changes in Medial Olivocochlear Strength Alters Auditory Pathway Development

Periodic spontaneous activity is a key feature of developing sensory systems, essential for the formation and refinement of neural circuits. Before the onset of hearing in altricial mammals, cochlear inner hair cells exhibit spontaneous electrical activity that activates primary afferents to propagate into the central nervous system. This activity, modulated by the medial olivocochlear efferent feedback via α9α10 nicotinic cholinergic receptors present in inner hair cells, is crucial for auditory system maturation. In this study, we examined the impact of sound exposure at levels below those causing hair cell damage during the critical developmental period by using genetically modified mice - α9 knockout and α9 knock-in models - with either absent or enhanced cholinergic activity. We further assessed how varying levels of medial olivocochlear feedback interact with early-age noise exposure to affect auditory development. Our findings reveal that both increased and absent olivocochlear activity result in altered auditory sensitivity at the onset of hearing and affect ribbon synapse number and morphology. Additionally, early exposure to loud noise caused long lasting changes in the inner ear of wild-type and α9 knockout mice, underscoring the heightened vulnerability during early development. In contrast, mice with enhanced cholinergic activity were protected from these changes. Overall, this work highlights the critical role of medial olivocochlear modulation in proper auditory system development and indicates that early noise exposure can interfere with normal cochlear maturation, resulting in pronounced long-term effects.