Dynamic REM Sleep Modulation by Ambient Temperature and the Critical Role of the Melanin-Concentrating Hormone System

Curr Biol. 2019 Jun 17;29(12):1976-1987.e4. doi: 10.1016/j.cub.2019.05.009. Epub 2019 May 30.


Ambient temperature (Ta) warming toward the high end of the thermoneutral zone (TNZ) preferentially increases rapid eye movement (REM) sleep over non-REM (NREM) sleep across species. The control and function of this temperature-induced REM sleep expression have remained unknown. Melanin-concentrating hormone (MCH) neurons play an important role in REM sleep control. We hypothesize that the MCH system may modulate REM sleep as a function of Ta. Here, we show that wild-type (WT) mice dynamically increased REM sleep durations specifically during warm Ta pulsing within the TNZ, compared to both the TNZ cool and baseline constant Ta conditions, without significantly affecting either wake or NREM sleep durations. However, genetically engineered MCH receptor-1 knockout (MCHR1-KO) mice showed no significant changes in REM sleep as a function of Ta, even with increased sleep pressure following a 4-h sleep deprivation. Using MCH-cre mice transduced with channelrhodopsin, we then optogenetically activated MCH neurons time locked with Ta warming, showing an increase in REM sleep expression beyond what Ta warming in yellow fluorescent protein (YFP) control mice achieved. Finally, in mice transduced with archaerhodopsin-T, semi-chronic optogenetic MCH neuronal silencing during Ta warming completely blocked the increase in REM sleep seen in YFP controls. These data demonstrate a previously unknown role for the MCH system in the dynamic output expression of REM sleep during Ta manipulation. These findings are consistent with the energy allocation hypothesis of sleep function, suggesting that endotherms have evolved neural circuits to opportunistically express REM sleep when the need for thermoregulatory defense is minimized.

Keywords: MCH; NREM sleep; REM sleep; energy allocation hypothesis; lateral hypothalamus; melanin-concentrating hormone; rapid eye movement sleep; resource optimization; sleep function; thermoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hypothalamic Hormones / metabolism*
  • Male
  • Melanins / metabolism*
  • Mice
  • Mice, Knockout
  • Neurons / physiology*
  • Pituitary Hormones / metabolism*
  • Sleep, REM / physiology*
  • Temperature*


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