An essential role for MEF2C in the cortical response to loss of sleep in mice

  1. Theresa E Bjorness
  2. Ashwinikumar Kulkarni
  3. Volodymyr Rybalchenko
  4. Ayako Suzuki
  5. Catherine Bridges
  6. Adam J Harrington
  7. Christopher W Cowan
  8. Joseph S Takahashi
  9. Genevieve Konopka  Is a corresponding author
  10. Robert W Greene  Is a corresponding author
  1. The University of Texas Southwestern Medical Center, United States
  2. University of Texas Southwestern Medical Center, United States
  3. Medical University of South Carolina, United States
  4. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States

Abstract

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss in C57BL/6J mice. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.

Data availability

The NCBI Gene Expression Omnibus (GEO) accession number for the RNA-seq data reported in this paper is GSE 144957

The following data sets were generated

Article and author information

Author details

  1. Theresa E Bjorness

    Department of Psychiatry & Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
  2. Ashwinikumar Kulkarni

    Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0951-2427
  3. Volodymyr Rybalchenko

    Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
  4. Ayako Suzuki

    Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
  5. Catherine Bridges

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    No competing interests declared.
  6. Adam J Harrington

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    No competing interests declared.
  7. Christopher W Cowan

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5472-3296
  8. Joseph S Takahashi

    Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0384-8878
  9. Genevieve Konopka

    Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    genevieve.konopka@utsouthwestern.edu
    Competing interests
    Genevieve Konopka, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3363-7302
  10. Robert W Greene

    Psychiatry, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    robertw.greene@utsouthwestern.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1355-9797

Funding

National Institute of Neurological Disorders and Stroke (NS103422)

  • Robert W Greene

International Institute for Integrative Sleep Medicine

  • Robert W Greene

National Institute of Mental Health (MH102603)

  • Robert W Greene

National Institute on Deafness and Other Communication Disorders (DC014702)

  • Genevieve Konopka

James S. McDonnell Foundation (220020467)

  • Genevieve Konopka

National Institute on Aging (AG045795)

  • Joseph S Takahashi

National Institute of Neurological Disorders and Stroke (NS106657)

  • Joseph S Takahashi

Howard Hughes Medical Institute

  • Joseph S Takahashi

National Institute of Mental Health (MH111464)

  • Christopher W Cowan

Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD098893)

  • Catherine Bridges

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

Reviewing Editor

  1. Anne E West, Duke University School of Medicine, United States

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 approved institutional animal care and use committee (IACUC) protocols (#102096) of the UT Southwestern Medical Center. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: April 27, 2020
  2. Accepted: August 26, 2020
  3. Accepted Manuscript published: August 27, 2020 (version 1)
  4. Version of Record published: September 14, 2020 (version 2)

Copyright

© 2020, Bjorness 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. Theresa E Bjorness
  2. Ashwinikumar Kulkarni
  3. Volodymyr Rybalchenko
  4. Ayako Suzuki
  5. Catherine Bridges
  6. Adam J Harrington
  7. Christopher W Cowan
  8. Joseph S Takahashi
  9. Genevieve Konopka
  10. Robert W Greene
(2020)
An essential role for MEF2C in the cortical response to loss of sleep in mice
eLife 9:e58331.
https://doi.org/10.7554/eLife.58331

Share this article

https://doi.org/10.7554/eLife.58331

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