Hernandez-Nunez Luis, Chen Alicia, Budelli Gonzalo, Berck Matthew E, Richter Vincent, Rist Anna, Thum Andreas S, Cardona Albert, Klein Mason, Garrity Paul, Samuel Aravinthan D T
Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Sci Adv. 2021 Aug 27;7(35). doi: 10.1126/sciadv.abg6707. Print 2021 Aug.
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 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.
体温稳态至关重要，且依赖于多种类型的冷敏和热敏细胞输出信号的整合。整合这些输出信号的计算过程尚不清楚。在这里，我们发现了一组热敏细胞（WCs），并表明这些WCs的输出信号与先前描述的冷敏细胞（CCs）在交叉抑制计算中相结合，以驱动幼虫的热稳态。WCs和CCs使用离子otropic受体的重叠组合来检测温度变化：WCs使用Ir68a、Ir93a和Ir25a，CCs使用Ir21a、Ir93a和Ir25a。WCs介导对升温的回避，同时交叉抑制对降温的回避，而CCs介导对降温的回避，同时交叉抑制对升温的回避。环境温度依赖性调节WC和CC介导的交叉抑制强度，使幼虫保持在其稳态设定点附近。通过神经生理学、定量行为分析和连接组学，我们展示了升温与降温途径之间灵活的整合如何协调稳态体温调节。
