1. Neuroscience

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

  1. Michelle M Frank
  2. Austen A Sitko
  3. Kirupa Suthakar
  4. Lester Torres Cadenas
  5. Mackenzie Hunt
  6. Mary Caroline Yuk
  7. Catherine Weisz
  8. Lisa V Goodrich  Is a corresponding author
  1. Harvard Medical School, United States
  2. National Institute on Deafness and Other Communication Disorders, United States
https://doi.org/10.7554/eLife.83855
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Cite this article
  1. Michelle M Frank
  2. Austen A Sitko
  3. Kirupa Suthakar
  4. Lester Torres Cadenas
  5. Mackenzie Hunt
  6. Mary Caroline Yuk
  7. Catherine Weisz
  8. Lisa V Goodrich
(2023)
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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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.

The following data sets were generated

Article and author information

Author details

  1. Michelle M Frank

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6613-8251

  2. Austen A Sitko

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7601-6143

  3. Kirupa Suthakar

    Section on Neuronal Circuitry, National Institute on Deafness and Other Communication Disorders, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Lester Torres Cadenas

    Section on Neuronal Circuitry, National Institute on Deafness and Other Communication Disorders, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Mackenzie Hunt

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Mary Caroline Yuk

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Catherine Weisz

    Section on Neuronal Circuitry, National Institute on Deafness and Other Communication Disorders, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2595-835X

  8. Lisa V Goodrich

    Department of Neurobiology, Harvard Medical School, Boston, United States
    For correspondence
    Lisa_Goodrich@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3331-8600

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.

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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  1. Michelle M Frank
  2. Austen A Sitko
  3. Kirupa Suthakar
  4. Lester Torres Cadenas
  5. Mackenzie Hunt
  6. Mary Caroline Yuk
  7. Catherine Weisz
  8. Lisa V Goodrich
(2023)
Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system
eLife 12:e83855.
https://doi.org/10.7554/eLife.83855

Share this article

https://doi.org/10.7554/eLife.83855

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