A new way to beat the heat

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Science Translational Medicine  12 Oct 2016:
Vol. 8, Issue 360, pp. 360ec163
DOI: 10.1126/scitranslmed.aai9160

As the days become shorter and the temperature drops, our warm clothes emerge once more. This is one of many adaptations that we use to maintain core body temperature within a narrow range. The neural pathways coordinating the responses to temperature changes and the biological details of these pathways remain to be delineated. Now, Tan et al. have identified cells and circuits in mice that respond to heat and regulate body temperature.

Previous publications suggested the involvement of the preoptic hypothalamic area (POA) in body temperature control. In their initial studies, Tan and coauthors enriched RNA from POA neurons switched on by heat and identified two neuropeptides that label the activated populations: pituitary adenylate cyclase-activating polypeptide (PACAP) and brain-derived neurotrophic factor (BDNF). Using in vivo imaging in mice, the researchers showed that PACAP and BDNF neurons are rapidly activated as the temperature increases, and the effect is mediated by heat-activated receptors in the skin. Next, the authors mimicked the effects of a higher temperature by switching on these neurons in the POA using optogenetics. Activating PACAP neurons rapidly decreased core body temperature through increased peripheral vasodilation and suppression of brown fat thermogenesis. However, these neurons also modified behavior: Nest-building and warm-seeking were greatly reduced when PACAP neurons were switched on, and mice found colder environments more rewarding.Last, the researchers showed that the PACAP neurons were connected to multiple CNS regions, including areas implicated in reward and those regulating the sympathetic nervous system. Activating the PACAP-expressing nerve terminals in one of these regions, the dorsomedial hypothalamus, was sufficient to reduce brown fat activation but did not alter vasodilation or behavior.

These studies suggest that in mice, a specific neural population in a small hypothalamic region controls many different responses to increasing temperature, from thermogenesis and vasodilation to behaviors such as nest-building. If these cells and circuits play a similar role in humans, it would be important to know how they are modulated in conditions, such as infection and thyroid disease, where body temperature is altered. In addition, it may eventually be possible to target such pathways to increase energy expenditure through thermogenesis and thus provide an additional approach to treating obesity.

C. L. Tan et al., Warm-sensitive neurons that control body temperature. Cell 167, 47–59 (2016). [Abstract]

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