Peptidergic neurons with extensive branching orchestrate the internal states and energy balance of male Drosophila melanogaster

Neuropeptide SIFamide (SIFa) neurons in Drosophila melanogaster have been characterized by their exceptionally elaborate arborization patterns, which extend from the brain into the ventral nerve cord (VNC). SIFa neurons are equipped to receive signals that integrate both internal physiological cues and external environmental stimuli. These signals enable the neurons to regulate energy balance, sleep patterns, metabolic status, and circadian timing. These peptidergic neurons are instrumental in orchestrating the animal’s internal states and refining its behavioral responses, yet the precise molecular underpinnings of this process remain elusive. Here we demonstrate that SIFa neurons coordinate a range of behavioral responses by selectively integrating inputs and outputs in a context-dependent manner. These neurons engage in a feedback loop with sNPF neurons in the ventral nerve cord, modifying behaviors such as long mating duration (LMD) and shorter mating duration (SMD). Furthermore, SIFa neurons receive essential inputs from neuropeptides Dsk, sNPF, and dilp2, which regulate interval timing behaviors. Activating SIFa neurons leads to reduced mating duration and increased food intake, while deactivating them reduces food intake. Overall, these findings demonstrate the importance of SIFa neurons in absorbing inputs and turning them into behavioral outputs, shedding light on animal’s intricate behavioral orchestration.