Non-rapid eye movement sleep determines resilience to social stress

  1. Brittany J Bush
  2. Caroline Donnay
  3. Eva-Jeneé A Andrews
  4. Darielle Lewis-Sanders
  5. Cloe L Gray
  6. Zhimei Qiao
  7. Allison J Brager
  8. Hadiya Johnson
  9. Hamadi CS Brewer
  10. Sahil Sood
  11. Talib Saafir
  12. Morris Benveniste
  13. Ketema N Paul
  14. J Christopher Ehlen  Is a corresponding author
  1. Morehouse School of Medicine, United States
  2. Walter Reed Army Institute of Research, United States
  3. University of California, Los Angeles, United States

Abstract

Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience. To examine if sleep has a determinative role in maladaptive behavioral-response to social stress, we investigated individual variations in resilience using a social-defeat model for male mice. Our results reveal a direct, causal relationship between sleep amount and resilience-demonstrating that sleep increases after social-defeat stress only occur in resilient mice. Further, we found that within the prefrontal cortex, a regulator of maladaptive responses to stress, pre-existing differences in sleep regulation predict resilience. Overall, these results demonstrate that increased NREM sleep, mediated cortically, is an active response to social-defeat stress that plays a determinative role in promoting resilience. They also show that differences in resilience are strongly correlated with inter-individual variability in sleep regulation.

Data availability

Data generated in this study are deposited in Dryad.

The following data sets were generated

Article and author information

Author details

  1. Brittany J Bush

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Caroline Donnay

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eva-Jeneé A Andrews

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Darielle Lewis-Sanders

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Cloe L Gray

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Zhimei Qiao

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Allison J Brager

    Behavioral Biology Branch, Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Hadiya Johnson

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Hamadi CS Brewer

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Sahil Sood

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Talib Saafir

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Morris Benveniste

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7070-1521
  13. Ketema N Paul

    Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0226-9559
  14. J Christopher Ehlen

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    For correspondence
    jehlen@msm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3223-9262

Funding

National Institute of General Medical Sciences (GM127260)

  • J Christopher Ehlen

National Institute on Minority Health and Health Disparities (Pilot funding,MD007602)

  • J Christopher Ehlen

National Institute of Neurological Disorders and Stroke (NS078410)

  • Ketema N Paul

National Heart, Lung, and Blood Institute (Graduate Student Fellowship,HL103104)

  • Brittany J Bush

National Heart, Lung, and Blood Institute (Graduate Student Fellowship,HL007901)

  • Eva-Jeneé A Andrews

National Heart, Lung, and Blood Institute (Postdoctoral Fellowship,HL117929)

  • Cloe L Gray

National Heart, Lung, and Blood Institute (Postdoctoral Fellowship,HL116077)

  • Allison J Brager

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 strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to a protocol (21-02) approved by the Morehouse School of Medicine institutional animal care and use committee (IACUC). All surgery was performed under isoflurane anesthesia, and analgesia was provided. Every effort was made to minimize pain and suffering.

Reviewing Editor

  1. Matthew N Hill, University of Calgary, Canada

Publication history

  1. Received: May 12, 2022
  2. Accepted: September 21, 2022
  3. Accepted Manuscript published: September 23, 2022 (version 1)
  4. Accepted Manuscript updated: September 26, 2022 (version 2)

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. Brittany J Bush
  2. Caroline Donnay
  3. Eva-Jeneé A Andrews
  4. Darielle Lewis-Sanders
  5. Cloe L Gray
  6. Zhimei Qiao
  7. Allison J Brager
  8. Hadiya Johnson
  9. Hamadi CS Brewer
  10. Sahil Sood
  11. Talib Saafir
  12. Morris Benveniste
  13. Ketema N Paul
  14. J Christopher Ehlen
(2022)
Non-rapid eye movement sleep determines resilience to social stress
eLife 11:e80206.
https://doi.org/10.7554/eLife.80206

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