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.

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.

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.

Metrics

  • 2,250
    views
  • 350
    downloads
  • 26
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Neuroscience
    Brian C Ruyle, Sarah Masud ... Jose A Morón
    Research Article

    Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.

    1. Neuroscience
    David C Williams, Amanda Chu ... Michael A McDannald
    Research Advance Updated

    Recognizing and responding to threat cues is essential to survival. Freezing is a predominant threat behavior in rats. We have recently shown that a threat cue can organize diverse behaviors beyond freezing, including locomotion (Chu et al., 2024). However, that experimental design was complex, required many sessions, and had rats receive many foot shock presentations. Moreover, the findings were descriptive. Here, we gave female and male Long Evans rats cue light illumination paired or unpaired with foot shock (eight total) in a conditioned suppression setting using a range of shock intensities (0.15, 0.25, 0.35, or 0.50 mA). We found that conditioned suppression was only observed at higher foot shock intensities (0.35 mA and 0.50 mA). We constructed comprehensive temporal ethograms by scoring 22,272 frames across 12 behavior categories in 200-ms intervals around cue light illumination. The 0.50 mA and 0.35 mA shock-paired visual cues suppressed reward seeking, rearing, and scaling, as well as light-directed rearing and light-directed scaling. These shock-paired visual cues further elicited locomotion and freezing. Linear discriminant analyses showed that ethogram data could accurately classify rats into paired and unpaired groups. Using complete ethogram data produced superior classification compared to behavior subsets, including an immobility subset featuring freezing. The results demonstrate diverse threat behaviors – in a short and simple procedure – containing sufficient information to distinguish the visual fear conditioning status of individual rats.