@article {Hernandez-Nunez2020.07.09.196428,
	title = {Synchronous and opponent thermosensors use flexible cross-inhibition to orchestrate thermal homeostasis},
	journal = {Science Advances},
	volume = {7},
	number = {35},
	year = {2021},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Body temperature homeostasis is an essential function that relies upon the integration of the outputs from multiple classes of cooling- and warming-responsive cells. The computations that integrate these diverse outputs to control body temperature are not understood. Here we discover a new set of Warming Cells (WCs), and show that the outputs of these WCs and previously described Cooling Cells (CCs1) are combined in a cross-inhibition computation to drive thermal homeostasis in larval Drosophila. We find that WCs and CCs are opponent sensors that operate in synchrony above, below, and near the homeostatic set-point, with WCs consistently activated by warming and inhibited by cooling, and CCs the converse. Molecularly, these opponent sensors rely on overlapping combinations of Ionotropic Receptors to detect temperature changes: Ir68a, Ir93a, and Ir25a for WCs; Ir21a, Ir93a, and Ir25a for CCs. Using a combination of optogenetics, sensory receptor mutants, and quantitative behavioral analysis, we find that the larva uses flexible cross-inhibition of WC and CC outputs to locate and stay near the homeostatic set-point. Balanced cross-inhibition near the set-point suppresses any directed movement along temperature gradients. Above the set-point, WCs mediate avoidance to warming while cross-inhibiting avoidance to cooling. Below the set-point, CCs mediate avoidance to cooling while cross-inhibiting avoidance to warming. Our results demonstrate how flexible cross-inhibition between warming and cooling pathways can orchestrate homeostatic thermoregulation.Competing Interest StatementThe authors have declared no competing interest.},
	doi = {10.1101/2020.07.09.196428},
	url = {https://www.science.org/doi/10.1126/sciadv.abg6707$\#$:~:text=DOI\%3A\%2010.1126/sciadv.abg6707},
	author = {Hernandez-Nunez, Luis and Chen, Alicia and Budelli, Gonzalo and Richter, Vincent and Rist, Anna and Thum, Andreas S. and Mason Klein and Garrity, Paul and Aravinthan D. T. Samuel}
}
