Behavioral state-dependent modulation of insulin-producing cells in Drosophila.

Insulin signaling plays a pivotal role in metabolic control and aging, and insulin accordingly is a key factor in several human diseases. Despite this importance, the in vivo activity dynamics of insulin-producing cells (IPCs) are poorly understood. Here, we characterized the effects of locomotion on the activity of IPCs in Drosophila. Using in vivo electrophysiology and calcium imaging, we found that IPCs were strongly inhibited during walking and flight and that their activity rebounded and overshot after cessation of locomotion. Moreover, IPC activity changed rapidly during behavioral transitions, revealing that IPCs are modulated on fast timescales in behaving animals. Optogenetic activation of locomotor networks ex vivo, in the absence of actual locomotion or changes in hemolymph sugar levels, was sufficient to inhibit IPCs. This demonstrates that the behavioral state-dependent inhibition of IPCs is actively controlled by neuronal pathways and is independent of changes in glucose concentration. By contrast, the overshoot in IPC activity after locomotion was absent ex vivo and after starvation, indicating that it was not purely driven by feedforward signals but additionally required feedback derived from changes in hemolymph sugar concentration. We hypothesize that IPC inhibition during locomotion supports mobilization of fuel stores during metabolically demanding behaviors, while the rebound in IPC activity after locomotion contributes to replenishing muscle glycogen stores. In addition, the rapid dynamics of IPC modulation support a potential role of insulin in the state-dependent modulation of sensorimotor processing.

PMID: 36580915 [PubMed - indexed for MEDLINE]