Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish

  1. Melanie Holmgren
  2. Michael E Ravicz
  3. Kenneth E Hancock
  4. Olga Strelkova
  5. Dorina Kallogjeri
  6. Artur A Indzhykulian
  7. Mark E Warchol
  8. Lavinia Sheets  Is a corresponding author
  1. Washington University School of Medicine in St Louis, United States
  2. Massachusetts Eye and Ear, United States
  3. Washington University School of Medicine in St. Louis, United States
  4. Harvard Medical School, United States
  5. Washington University School of Medicine, United States

Abstract

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4 , and 7.

Article and author information

Author details

  1. Melanie Holmgren

    Otolaryngology-Head & Neck Surgery, Washington University School of Medicine in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael E Ravicz

    Eaton Peabody Laboratory, Massachusetts Eye and Ear, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9978-3444
  3. Kenneth E Hancock

    Eaton Peabody Laboratory, Massachusetts Eye and Ear, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Olga Strelkova

    Eaton Peabody Laboratory, Massachusetts Eye and Ear, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dorina Kallogjeri

    Washington University School of Medicine in St. Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Artur A Indzhykulian

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

    Departments of Otolaryngology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Lavinia Sheets

    Department of Otolaryngology, Washington University School of Medicine in St Louis, St Louis, United States
    For correspondence
    sheetsl@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5231-2450

Funding

National Institute on Deafness and Other Communication Disorders (R01DC016066)

  • Lavinia Sheets

National Institute on Deafness and Other Communication Disorders (R01DC017166)

  • Artur A Indzhykulian

National Institute on Deafness and Other Communication Disorders (R01DC006283)

  • Mark E Warchol

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 with the approval of the Institutional Animal Care and Use Committee of Washington University School of Medicine in St. Louis (protocol no. 20-0158) and in accordance with NIH guidelines for use of zebrafish.

Copyright

© 2021, Holmgren et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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https://doi.org/10.7554/eLife.69264

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