Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize murine OCNs during postnatal development, in mature animals, and after sound exposure. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.

Automated summary

We characterized murine brainstem olivocochlear neurons (OCNs) during postnatal development, in mature animals, and after sound exposure using single-nucleus sequencing, anatomical reconstructions, and electrophysiology. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes and found that they express distinct physiologically relevant genes that change over development. We also discovered a neuropeptide-enriched LOC subtype producing Neuropeptide Y along with other neurotransmitters. Acoustic trauma leads to strong upregulation of LOC neuropeptide expression, potentially providing sustained cochlear protection. OCNs have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.