4.8 Article

A synaptic temperature sensor for body cooling

Journal

NEURON
Volume 109, Issue 20, Pages 3283-+

Publisher

CELL PRESS
DOI: 10.1016/j.neuron.2021.10.001

Keywords

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Funding

  1. Ministry of Science, Research and the Arts Baden-Wurttemberg (MWK)
  2. German Research Foundation (DFG) [INST 35/1314-1 FUGG]
  3. European Research Council [ERC-CoG-772395]
  4. German Research Foundation [SFB/TRR152, SFB1158]
  5. Boehringer Ingelheim Foundation
  6. Physician Scientist Program of the Medical Faculty of Heidelberg
  7. Chica and Heinz Schaller Foundation
  8. NARSAD

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Research has identified a synaptic mechanism that regulates temperature sensitivity, enhancing the temperature response of warm-sensitive neurons at the cellular level through TRPM2 ion channels. This mechanism facilitates thermoregulation by linking WSN function with body temperature regulation.
Deep brain temperature detection by hypothalamic warm-sensitive neurons (WSNs) has been proposed to provide feedback information relevant for thermoregulation. WSNs increase their action potential firing rates upon warming, a property that has been presumed to rely on the composition of thermosensitive ion channels within WSNs. Here, we describe a synaptic mechanism that regulates temperature sensitivity of preoptic WSNs and body temperature. Experimentally induced warming of the mouse hypothalamic preoptic area in vivo triggers body cooling. TRPM2 ion channels facilitate this homeostatic response and, at the cellular level, enhance temperature responses of WSNs, thereby linking WSN function with thermoregulation for the first time. Rather than acting within WSNs, we-unexpectedly-find TRPM2 to temperature-dependently increase synaptic drive onto WSNs by disinhibition. Our data emphasize a network-based interoceptive paradigm that likely plays a key role in encoding body temperature and that may facilitate integration of diverse inputs into thermoregulatory pathways.

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