Warm-Sensitive Neurons that Control Body Temperature

Cell. 2016 Sep 22;167(1):47-59.e15. doi: 10.1016/j.cell.2016.08.028. Epub 2016 Sep 8.


Thermoregulation is one of the most vital functions of the brain, but how temperature information is converted into homeostatic responses remains unknown. Here, we use an unbiased approach for activity-dependent RNA sequencing to identify warm-sensitive neurons (WSNs) within the preoptic hypothalamus that orchestrate the homeostatic response to heat. We show that these WSNs are molecularly defined by co-expression of the neuropeptides BDNF and PACAP. Optical recordings in awake, behaving mice reveal that these neurons are selectively activated by environmental warmth. Optogenetic excitation of WSNs triggers rapid hypothermia, mediated by reciprocal changes in heat production and loss, as well as dramatic cold-seeking behavior. Projection-specific manipulations demonstrate that these distinct effectors are controlled by anatomically segregated pathways. These findings reveal a molecularly defined cell type that coordinates the diverse behavioral and autonomic responses to heat. Identification of these warm-sensitive cells provides genetic access to the core neural circuit regulating the body temperature of mammals. PAPERCLIP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Body Temperature Regulation / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Gene Expression Regulation*
  • Hot Temperature*
  • Mice
  • Microdissection
  • Neurons / metabolism
  • Neurons / physiology*
  • Optogenetics
  • Pituitary Adenylate Cyclase-Activating Polypeptide / genetics*
  • RNA, Messenger / genetics
  • Ribosomal Protein S6 / metabolism
  • Sequence Analysis, RNA
  • Ventromedial Hypothalamic Nucleus / cytology*
  • Ventromedial Hypothalamic Nucleus / metabolism


  • Brain-Derived Neurotrophic Factor
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • RNA, Messenger
  • Ribosomal Protein S6