Opponent thermosensory cells use flexible cross-inhibition for context-dependent choice in Drosophila thermotaxis

Animals often use sensory cells with opposing polarity that are separately tuned to detect increments or decrements of environmental stimuli. For example, cooling and warming cells detect temperature changes; moist and dry cells detect humidity changes; and ON-OFF retinal cells detect luminance changes. How animals integrate the outputs of opponent cells to navigate towards favorable points along a sensory gradient from higher or lower points remains poorly understood. Here, we show how the outputs of warming cells (WCs) and cooling cells (CCs) in the larva are combined to produce context-dependent thermotactic navigation. The newly discovered WCs and the previously described CCs require distinct but overlapping sets of Ionotropic Receptors to sense temperature changes: Ir68a, Ir93a, and Ir25a for WCs; Ir21a, Ir93a, and Ir25a for CCs. WCs and CCs are bidirectional opponent sensors: WCs are activated by warming and inhibited by cooling, whereas CCs are activated by cooling and inhibited by warming. Both WCs and CCs are sensitive to temperature changes from high temperatures where the larva avoids warming to low temperatures where it avoids cooling. However, at all temperatures, optogenetically-imposed fictive warming of the WCs as well as fictive cooling of the CCs evoke avoidance responses, and fictive cooling of the WCs as well as fictive warming of the CCs inhibit avoidance responses. We reconcile these sensory properties and behavioral responses by showing that the larva uses flexible cross-inhibition of the output pathways of WCs and CCs when making perceptual choices during thermotaxis. Balanced cross-inhibition near preferred temperatures suppresses any directed movement on temperature gradients. Above preferred temperatures, WCs mediate avoidance to warming while cross-inhibiting avoidance to cooling. Below preferred temperatures, CCs mediate avoidance to cooling while cross-inhibiting avoidance to warming. Our results show how flexible cross-inhibition orchestrates a context-dependent perceptual choice during a navigational behavior.