A neuroendocrine feedback loop inC. elegansmales integrates food detection and biological sex to modulate chemoreceptor expression and behavioral flexibility

SUMMARYDynamic integration of internal and external cues is essential for flexible, adaptive animal behavior. InC. elegans, biological sex and feeding state regulate expression of the food-associated chemoreceptorodr-10, contributing to plasticity in food detection and the decision between feeding and exploration. In adult hermaphrodites,odr-10expression is high; in well-fed adult males,odr-10expression is low, promoting exploratory mate-searching behavior. Food-deprivation transiently activates maleodr-10expression, heightening food sensitivity and reducing food-leaving. Here, we identify a neuroendocrine feedback loop that sex-specifically regulatesodr-10in response to food deprivation. In well-fed males, insulin-like (IIS) and TGFβ signaling repressodr-10expression. Upon food deprivation,odr-10is directly activated by DAF-16/FoxO, the canonicalC. elegansIIS effector. The TGFβ ligand DAF-7 acts upstream of IIS, and, likely because of its sexually dimorphic expression in the nervous system, links feeding toodr-10only in males. Surprisingly, these responses to food deprivation are not triggered by internal metabolic cues, but rather by the loss of sensory signals from food. In the presence of inedible food, males become metabolically starved but express levels ofodr-10anddaf-7comparable to those of well-fed males. Further, exposing food-deprived males to inedible food is sufficient to restore lowodr-10expression. Food signals are detected by a small number of sensory neurons whose activity non-autonomously regulatesdaf-7expression, IIS, andodr-10. Thus, adultC. elegansmales employ a neuroendocrine feedback loop that integrates food detection and genetic sex to dynamically modulate chemoreceptor expression and sensory behavior.