Coordination of neuropeptide signaling in the Drosophila clock output network

The Drosophila clock network is a network of peptidergic oscillators, with neuropeptides coordinating network activity and conveying time-of-day information to circadian output regions that regulate circadian behavior and physiology. While connectivity within the clock network is well-established, how the clock conveys time-of-day information to output regions remains unknown. Both clock neurons, and neurons within the pars intercerebralis (PI), a major circadian output hub, secrete multiple neuropeptides and small molecule neurotransmitters that may work in concert. Using clock-neuron-specific CRISPR, we have identified novel output neuropeptides that play sex-specific roles in regulating circadian rest-activity behavior. Clock neurons provide time-of-day specific signals to the PI via both neuropeptides and small molecule neurotransmitters. Further, we have identified intra-PI connectivity which allows integration of time-of-day cues with additional sensory inputs to guide appropriate behavior selection in complex environments.