A synaptic temperature sensor for body cooling

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. [Display omitted] •Temperature in the hypothalamic preoptic area (POA) tracks body temperature in mice•TRPM2 participates in warmth detection in the POA in vivo•Presynaptic TRPM2 detects temperature increases to activate warm-sensitive neurons•Warming enhances inhibitory transmitter release via TRPM2 to mediate disinhibition Kamm, Boffi, et al. found that the ion channel TRPM2 mediates detection of warm temperatures in the mouse hypothalamus. Specifically, TRPM2 enhances the thermosensitivity of hypothalamic warm-sensitive neurons (WSNs) via a presynaptic mechanism. This study highlights the role of WSNs and TRPM2 in body temperature homeostasis under hot environments.