Synchronous and opponent thermosensors use flexible cross-inhibition to orchestrate thermal homeostasis

Body temperature homeostasis is essential and reliant upon the integration of outputs from multiple classes of cooling-and warming-responsive cells. The computations that integrate these outputs are not understood. Here, we discover a set of warming cells (WCs) and show that the outputs of these WCs combine with previously described cooling cells (CCs) in a cross-inhibition computation to drive thermal homeostasis in larval Drosophila. WCs and CCs detect temperature changes using overlapping combinations of ionotropic receptors: Ir68a, Ir93a, and Ir25a for WCs and Ir21a, Ir93a, and Ir25a for CCs. WCs mediate avoidance to warming while cross-inhibiting avoidance to cooling, and CCs mediate avoidance to cooling while cross-inhibiting avoidance to warming. Ambient temperature-dependent regulation of the strength of WC- and CC-mediated cross-inhibition keeps larvae near their homeostatic set point. Using neurophysiology, quantitative behavioral analysis, and connectomics, we demonstrate how flexible integration between warming and cooling pathways can orchestrate homeostatic thermoregulation.

Automated summary

This study reveals the interaction between warming cells and cooling cells in larval Drosophila, which is crucial for maintaining thermal homeostasis. The integration of warming and cooling pathways through ionotropic receptors allows for the flexible regulation of body temperature set point. The cross-inhibition computation between warming and cooling cells orchestrates homeostatic thermoregulation in larvae.