Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila

Starvation induces sustained increase in locomotion, which facilitates food localization and acquisition and hence composes an important aspect of food-seeking behavior. We investigated how nutritional states modulated starvation-induced hyperactivity in adult Drosophila. The receptor of the adipokinetic hormone (AKHR), the insect analog of glucagon, was required for starvation-induced hyperactivity. AKHR was expressed in a small group of octopaminergic neurons in the brain. Silencing AKHR neurons and blocking octopamine signaling in these neurons eliminated starvation-induced hyperactivity, whereas activation of these neurons accelerated the onset of hyperactivity upon starvation. Neither AKHR nor AKHR neurons were involved in increased food consumption upon starvation, suggesting that starvation-induced hyperactivity and food consumption are independently regulated. Single cell analysis of AKHR neurons identified the co-expression of Drosophila insulin-like receptor (dlnR), which imposed suppressive effect on starvation-induced hyperactivity. Therefore, insulin and glucagon signaling exert opposite effects on starvation-induced hyperactivity via a common neural target in Drosophila.