Optogenetic Stimulation of MCH Neurons Increases Sleep
- Roda Rani Konadhode2,*,
- Dheeraj Pelluru2,*,
- Carlos Blanco-Centurion2,
- Andrew Zayachkivsky4,
- Meng Liu2,
- Thomas Uhde2,
- W. Bailey Glen Jr3,
- Anthony N. van den Pol4,
- Patrick J. Mulholland2,3, and
- Priyattam J. Shiromani1,2
- 1Ralph H. Johnson VA Medical Center,
- 2Departments of Psychiatry and Behavioral Sciences, and
- 3Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, and
- 4Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520
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Author contributions: A.N.v.d.P., P.J.M., and P.J.S. designed research; R.R.K., D.P., C.B.-C., A.Z., M.L., W.B.G., and P.J.M. performed research; T.U. and A.N.v.d.P. contributed unpublished reagents/analytic tools; R.R.K., D.P., C.B.-C., M.L., W.B.G., A.N.v.d.P., P.J.M., and P.J.S. analyzed data; A.N.v.d.P. and P.J.S. wrote the paper.
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↵*R.R.K. and D.P. contributed equally to this work.
Abstract
Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.
- Received March 21, 2013.
- Revision received April 16, 2013.
- Accepted May 14, 2013.
- Copyright © 2013 the authors 0270-6474/13/3310257-07$15.00/0
