A Neuronal Hub Binding Sleep Initiation and Body Cooling in Response to a Warm External Stimulus

Curr Biol. 2018 Jul 23;28(14):2263-2273.e4. doi: 10.1016/j.cub.2018.05.054. Epub 2018 Jul 12.


Mammals, including humans, prepare for sleep by nesting and/or curling up, creating microclimates of skin warmth. To address whether external warmth induces sleep through defined circuitry, we used c-Fos-dependent activity tagging, which captures populations of activated cells and allows them to be reactivated to test their physiological role. External warming tagged two principal groups of neurons in the median preoptic (MnPO)/medial preoptic (MPO) hypothalamic area. GABA neurons located mainly in MPO produced non-rapid eye movement (NREM) sleep but no body temperature decrease. Nitrergic-glutamatergic neurons in MnPO-MPO induced both body cooling and NREM sleep. This circuitry explains how skin warming induces sleep and why the maximal rate of core body cooling positively correlates with sleep onset. Thus, the pathways that promote NREM sleep, reduced energy expenditure, and body cooling are inextricably linked, commanded by the same neurons. This implies that one function of NREM sleep is to lower brain temperature and/or conserve energy.

Keywords: NOS1; TetTagging; anesthesia; energy balance; hypothermia; sedation; sleep; thermoregulation; torpor; warm stimulus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Body Temperature Regulation / physiology*
  • Cold Temperature
  • Hot Temperature
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Preoptic Area / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Sleep / physiology*


  • Proto-Oncogene Proteins c-fos