An essential role for MEF2C in the cortical response to loss of sleep in mice
- The University of Texas Southwestern Medical Center, United States
- University of Texas Southwestern Medical Center, United States
- Medical University of South Carolina, United States
- 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
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An essential role for MEF2C in the cortical response to loss of sleepNCBI Gene Expression Omnibus, GSE144957.
Article and author information
Author details
Ashwinikumar Kulkarni
Christopher W Cowan
Joseph S Takahashi
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.
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.
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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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
