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

Abstract

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.

The connectome of an insect brain

“…We found that most 2nd-order neurons received direct input from a single SN type (Fig. 4B), with some exceptions, including olfactory local neurons that also received from gustatory and thermo warm SNs, as previously reported ( 45, 48 ). 3rd-order neurons were more often shared across modalities and, by the 4th-order, most neurons were shared across modalities (Fig.…”

“…We classified input neurons based on their known sensory modalities. Olfactory ( 45 ), gustatory ( 47, 66, 101 ), thermosensory ( 48, 102 ), visual ( 46 ), gut ( 47, 103, 104 ) and respiratory state SNs ( 105 ) project directly to the brain. Somatosensory ANs from the nerve cord received direct or indirect input from mechanosensory ( 29, 38, 106 ), nociceptive ( 38, 107–109 ) and proprioceptive SNs ( 110, 111 ) (Fig.…”

“…We mapped all neurons in the brain using computer-assisted reconstruction with CATMAID (39,40) in a previously acquired nanometer-resolution EM volume of the central nervous system (CNS) of the Drosophila larva (38) and we annotated their synapses. Prior studies have used the same EM volume to map sensory and premotor circuits in the ventral nerve cord (VNC) and subesophageal zone (SEZ) (38,(41)(42)(43)(44), as well specific subregions in the brain (a total of 452 sensory and 1054 brain neurons): the primary sensory neuropils (45)(46)(47)(48)(49) and the higher order center for learning and memory (the mushroom body, MB) (25,31,34). Here, we took a dense circuit mapping approach to reconstruct the remaining 1507 brain neurons.…”

Cool and warm ionotropic receptors control multiple thermotaxes in Drosophila larvae

“…Both cool and warm IR receptors are sufficient for cool preferences between 18 • C and 25 • C IR25a and IR93a are co-receptor IRs for both cool and warm receptors (Knecht et al, 2016;Ni et al, 2016;Hernandez-Nunez et al, 2021). To confirm the function of IR25a and IR93a in 18 • C preferences, we performed rescue experiments.…”

Neural Circuits Underlying Behavioral Flexibility: Insights From Drosophila

“…We focus specifically on studies of adult Drosophila . There are a number of articles describing behavioral flexibility in Drosophila larvae that are not discussed here (e.g., Schroll et al, 2006 ; Schleyer et al, 2011 , 2020 ; Allen et al, 2017 ; Mancini et al, 2019 ; Eschbach et al, 2020 ; Miroschnikow et al, 2020 ; Slankster et al, 2020 ; Gowda et al, 2021 ; Hernandez-Nunez et al, 2021 ; Vogt et al, 2021 ). Our goal is to highlight generalizable neural circuitry frameworks for how sensory cues, state, and experience are integrated to guide the flexible selection of appropriate behavior.…”