Neuropeptides in Neural Circuits and Behavior

Abstract

Neurons comprise major elements of the nervous system, but do not function in isolation. All nervous system function requires neurons to communicate with each other to integrate, relay, and output information. Neuropeptides are a class of signaling molecules commonly used throughout the nervous system to transfer information between neurons; however, their actions in neuronal circuits and roles in behavior are less understood compared to those of small molecule neurotransmitters. To examine the role of neuropeptides in circuits and behavior we performed two complementary studies. To investigate the role of neuropeptides in neural circuits, we studied how neuropeptides might influence primary olfactory circuit function. We find that all olfactory neurons investigated within a single Drosophila olfactory microcircuit contain dense-core vesicles (DCVs), suggesting that most olfactory neurons express neuropeptides in addition to neurotransmitters. We show that many DCVs localize to presynaptic sites, suggesting that co-transmission of neurotransmitters and neuropeptides plays a prevalent role in this circuit. We find that projection neuron (PN) presynaptic sites contain more DCVs than expected by chance when olfactory receptor neurons (ORNs) are postsynaptic. These data suggest that PNs may use neuropeptides to regulate signaling within a single olfactory channel. This provides an additional modulatory mechanism that can increase the flexibility of olfactory circuit function. We also explored how neuropeptides influence behavior by identifying a novel role for a neuropeptide in sleep behavior. We find that the neuropeptide Corazonin (Crz) is released from ~14 neurons in the pars lateralis to promote wake behavior in Drosophila. We show that the cell cycle protein, Cyclin A, localizes to presynaptic sites within these cells and promotes wake likely via Crz release. In addition, we provide evidence that Cyclin A functions with other repurposed cell cycle machinery to promote wake. Finally, we find that these cells integrate signals from several wake-promoting neuropeptides. This work identifies a novel network of sleep molecules, including the neuropeptide Corazonin, and an integrating center of wake-promoting signals. Together, these studies provide valuable insight into the role of neuropeptides in circuit function and behavior.