Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system
- Harvard Medical School, United States
- National Institute on Deafness and Other Communication Disorders, United States
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.
Data availability
Single-cell data collected in this study is available on GEO, accession number GSE214027.
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Single-nucleus sequencing data from developing and adult mouse olivocochlear neuronsNCBI Gene Expression Omnibus, GSE214027.
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (R01-DC015974)
- Lisa V Goodrich
National Institute on Deafness and Other Communication Disorders (R01-DC009223)
- Lisa V Goodrich
NIH Office of the Director (Z01-DC000091)
- Catherine Weisz
Blavatnik Family Foundation (Blavatnik Sensory Disorders Research Grant)
- Lisa V Goodrich
National Institute on Deafness and Other Communication Disorders (F32-DC019009)
- Austen A Sitko
Harvard Mahoney Neuroscience Institute Fund (Postdoctoral Fellowship)
- Austen A Sitko
Amgen Foundation (Summer Fellowship)
- Mary Caroline Yuk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with recommendations from the Guide for the Care and Use of Laboratory Animals. All experiments and procedures were approved by the Institutional Care and Use Committee of Harvard Medical School (protocol #IS00000067) or the National Institute on Deafness and Other Communication Disorders Animal Care and Use Committee. Every effort was made to minimize suffering throughout this work.
Reviewing Editor
- Catherine Emily Carr, University of Maryland, United States
Publication history
- Received: September 30, 2022
- Accepted: March 3, 2023
- Accepted Manuscript published: March 6, 2023 (version 1)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system
eLife 12:e83855.
https://doi.org/10.7554/eLife.83855
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