Medial olivocochlear activity modulates central auditory synapse structure and function

Before hearing onset, inner hair cells in altricial mammals show spontaneous electrical activity crucial for proper auditory pathway development. This activity is finely regulated by descending efferent nerves from the central nervous system during a critical developmental period, ensuring precise auditory circuit formation. By combining electrophysiology with ultrastructural analyses, our study shows that genetically manipulating efferent function—either by eliminating it or enhancing it—leads to structural alterations and severe synaptic dysfunction in the calyx of Held—principal neurons of the medial nucleus of the trapezoid body (MNTB) synapse within the auditory brainstem. These results indicate that transient, well-regulated efferent control of cochlear activity is crucial for establishing accurate central auditory connectivity. Importantly, enhancing efferent peripheral activity causes more pronounced central synaptic changes than its absence, highlighting the importance of balanced efferent modulation during early auditory system development for normal brainstem auditory function.