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

Author:

Frank Michelle M1ORCID,Sitko Austen A1ORCID,Suthakar Kirupa2,Torres Cadenas Lester2,Hunt Mackenzie1,Yuk Mary Caroline1,Weisz Catherine JC2ORCID,Goodrich Lisa V1ORCID

Affiliation:

1. Department of Neurobiology, Harvard Medical School

2. Section on Neuronal Circuitry, National Institute on Deafness and Other Communication Disorders

Abstract

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.

Funder

National Institute on Deafness and Other Communication Disorders

NIH Office of the Director

Blavatnik Family Foundation

Harvard Mahoney Neuroscience Institute Fund

Amgen Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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