Research Article

The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia

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Science  25 Aug 2016:
aaf7537
DOI: 10.1126/science.aaf7537

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Abstract

Body temperature homeostasis is critical for survival and requires precise regulation by the nervous system. The hypothalamus serves as principal thermostat that detects and regulates internal temperature. We demonstrate that the ion channel TRPM2 is a temperature sensor in a subpopulation of hypothalamic neurons. TRPM2 limits the fever response, and may detect increased temperatures to prevent overheating. Furthermore, chemogenetic activation or inhibition of hypothalamic TRPM2-expressing neurons in vivo decreased and increased body temperature, respectively. Such manipulation may allow analysis of the beneficial effects of altered body temperature on diverse disease states. Identification of a functional role for TRP channels in monitoring internal body temperature should promote further analysis of molecular mechanisms governing thermoregulation and foster the genetic dissection of hypothalamic circuits concerned with temperature homeostasis.

  • * Present Address: Max Delbrück Center for Molecular Medicine, Robert Rössle Straße 10, 13125 Berlin, Germany.

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