Neural signatures of auditory hypersensitivity following acoustic trauma

Abstract

Neurons in sensory cortex exhibit a remarkable capacity to maintain stable firing rates despite large fluctuations in afferent activity levels. However, sudden peripheral deafferentation in adulthood can trigger an excessive, non-homeostatic cortical compensatory response that may underlie perceptual disorders including sensory hypersensitivity, phantom limb pain, and tinnitus. Here, we show that mice with noise-induced damage of the high-frequency cochlear base were behaviorally hypersensitive to spared mid-frequency tones and to direct optogenetic stimulation of auditory thalamocortical neurons. Chronic 2-photon calcium imaging from ACtx pyramidal neurons (PyrNs) revealed an initial stage of spatially diffuse hyperactivity, hyper-correlation, and auditory hyperresponsivity that consolidated around deafferented map regions three or more days after acoustic trauma. Deafferented PyrN ensembles also displayed hypersensitive decoding of spared mid-frequency tones that mirrored behavioral hypersensitivity, suggesting that non-homeostatic regulation of cortical sound intensity coding following sensorineural loss may be an underlying source of auditory hypersensitivity. Excess cortical response gain after acoustic trauma was expressed heterogeneously among individual PyrNs, yet 40% of this variability could be accounted for by each cell's baseline response properties prior to acoustic trauma. PyrNs with initially high spontaneous activity and gradual monotonic intensity growth functions were more likely to exhibit non-homeostatic excess gain after acoustic trauma. This suggests that while cortical gain changes are triggered by reduced bottom-up afferent input, their subsequent stabilization is also shaped by their local circuit milieu, where indicators of reduced inhibition can presage pathological hyperactivity following sensorineural hearing loss.

Data availability

All Figure code and data will be available on the Harvard Dataverse at the following:doi:10.7910/DVN/JLIKOZ

The following data sets were generated

Article and author information

Author details

  1. Matthew McGill

    Division of Medical Sciences, Harvard Medical School, Boston, United States
    For correspondence
    mmcgill@g.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2322-9580
  2. Ariel E Hight

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yurika L Watanabe

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Aravindakshan Parthasarathy

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dongqin Cai

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kameron Clayton

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kenneth E Hancock

    Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Anne Takesian

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Sharon G Kujawa

    Department of Otolaryngology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Daniel B Polley

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5120-2409

Funding

National Institute on Deafness and Other Communication Disorders (DC018974-02)

  • Matthew McGill

National Institute on Deafness and Other Communication Disorders (DC014871)

  • Ariel E Hight

Nancy Lurie Marks Family Foundation

  • Anne Takesian
  • Daniel B Polley

National Institute on Deafness and Other Communication Disorders (DC009836)

  • Daniel B Polley

National Institute on Deafness and Other Communication Disorders (DC015857)

  • Sharon G Kujawa
  • Daniel B Polley

National Institute on Deafness and Other Communication Disorders (DC018353)

  • Anne Takesian

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Brice Bathellier, CNRS, France

Ethics

Animal experimentation: All procedures were approved by the Massachusetts Eye and Ear Animal Care and Use Committee and followed the guidelines established by the National Institute of Health for the care and use of laboratory animals.

Human subjects: The study was approved by the human subjects Institutional Review Board at Mass General Brigham and Massachusetts Eye and Ear. Data analysis was performed on de-identified data, in accordance with the relevant guidelines and regulations.

Version history

  1. Received: May 5, 2022
  2. Preprint posted: May 25, 2022 (view preprint)
  3. Accepted: September 14, 2022
  4. Accepted Manuscript published: September 16, 2022 (version 1)
  5. Version of Record published: October 12, 2022 (version 2)

Copyright

© 2022, McGill 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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  1. Matthew McGill
  2. Ariel E Hight
  3. Yurika L Watanabe
  4. Aravindakshan Parthasarathy
  5. Dongqin Cai
  6. Kameron Clayton
  7. Kenneth E Hancock
  8. Anne Takesian
  9. Sharon G Kujawa
  10. Daniel B Polley
(2022)
Neural signatures of auditory hypersensitivity following acoustic trauma
eLife 11:e80015.
https://doi.org/10.7554/eLife.80015

Share this article

https://doi.org/10.7554/eLife.80015

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