An essential role for MEF2C in the cortical response to loss of sleep in mice
Theresa E Bjorness,
Ashwinikumar Kulkarni,
Volodymyr Rybalchenko,
Ayako Suzuki,
Catherine Bridges,
Adam J Harrington,
Christopher W Cowan,
Joseph S Takahashi,
Genevieve Konopka,
Robert W Greene
Affiliations
Theresa E Bjorness
Department of Psychiatry, Peter O’Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, United States; Research Service, North Texas VA Health Care System, Dallas, United States
Department of Neuroscience, Peter O’Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
Department of Psychiatry, Peter O’Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, United States; Department of Neuroscience, Peter O’Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, United States; International Institute of Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Japan
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.
