Optogenetic stimulation of MCH neurons increases sleep

J Neurosci. 2013 Jun 19;33(25):10257-63. doi: 10.1523/JNEUROSCI.1225-13.2013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Channelrhodopsins
  • Circadian Rhythm / physiology
  • Color
  • Delta Rhythm / physiology
  • Electrodes, Implanted
  • Electroencephalography
  • Hypothalamic Hormones / genetics*
  • Hypothalamic Hormones / physiology*
  • Hypothalamus / physiology
  • Immunohistochemistry
  • Melanins / genetics*
  • Melanins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Pituitary Hormones / genetics*
  • Pituitary Hormones / physiology*
  • Plasmids / genetics
  • Sleep / physiology*
  • Sleep, REM / physiology
  • Wakefulness / physiology

Substances

  • Channelrhodopsins
  • Hypothalamic Hormones
  • Melanins
  • Pituitary Hormones
  • melanin-concentrating hormone