A nutrient-specific gut hormone arbitrates between courtship and feeding

Animals must set behavioral priority in a context-dependent manner and switch from one behavior to another at the appropriate moment. Here we probe the molecular and neuronal mechanisms that orchestrate the transition from feeding to courtship in Drosophila. We find that feeding is prioritized over courtship in starved males, and the consumption of protein-rich food rapidly reverses this order within a few minutes. At the molecular level, a gut-derived, nutrient-specific neuropeptide hormone — Diuretic hormone 31 (Dh31) — is both necessary and sufficient to induce a switch from feeding to courtship. We further address the underlying kinetics with calcium imaging experiments. Amino acids from food acutely activate Dh31(+) enteroendocrine cells in the gut, elevating Dh31 levels in circulation. In addition, three-photon functional imaging of intact flies shows that optogenetic stimulation of Dh31(+) enteroendocrine cells rapidly excites a subset of brain neurons that express Dh31 receptor (Dh31R). Gut-derived Dh31 excites the brain neurons through the circulatory system within a few minutes, a speed in line with the feeding-courtship behavioral switch. At the circuit level, there are two distinct populations of Dh31R(+) neurons in the brain, with one population inhibiting feeding through allatostatin-C and the other promoting courtship through corazonin. Together, our findings illustrate an elegant mechanism by which the consumption of protein-rich food triggers the release of a gut hormone which in turn prioritizes courtship over feeding through two distinct pathways.