Gain Control of Peripheral Input by Core Brain Thermosensors Drives Drosophila Thermoregulation

Temperature affects all aspects of animal physiology, rendering thermoregulation critical for survival. In Drosophila larvae, well-established peripheral thermosensors detect temperature changes and mediate thermotaxis over a broad innocuous range, but how larvae seek a specific preferred body temperature within this range remains unknown. Here we show that core thermosensors in the brain (LPBT neurons) establish this setpoint by mediating warming-evoked turning at temperatures above it. LPBTs express the warmth-activated thermosensor TrpA1(A), but are not simply cell-autonomous thermosensors. Rather, sustained LPBT responses above setpoint require both peripheral thermosensory input and TRPA1-dependent thermosensing within LPBTs. TRPA1-dependent core thermosensing provides gain control that defines the homeostatic setpoint by tuning the behavioral weights of peripheral inputs. This new conception of thermal preference reveals parallels between Drosophila and mammalian thermoregulation.