Drosulfakinin signaling in fruitless circuitry antagonizes P1 neurons to regulate sexual arousal in Drosophila

Shunfan Wu,Yan Liu,Caihong Han,Huanhuan Qiao,Yufeng Pan,Qionglin Peng,Huan Zhao,Shengzhan D Luo,Mengshi Sun,Ping Peng,Chao Guo,Jie Chen

doi:10.1038/s41467-019-12758-6

Abstract

Animals perform or terminate particular behaviors by integrating external cues and internal states through neural circuits. Identifying neural substrates and their molecular modulators promoting or inhibiting animal behaviors are key steps to understand how neural circuits control behaviors. Here, we identify the Cholecystokinin-like peptide Drosulfakinin (DSK) that functions at single-neuron resolution to suppress male sexual behavior in Drosophila. We found that Dsk neurons physiologically interact with male-specific P1 neurons, part of a command center for male sexual behaviors, and function oppositely to regulate multiple arousal-related behaviors including sex, sleep and spontaneous walking. We further found that the DSK-2 peptide functions through its receptor CCKLR-17D3 to suppress sexual behaviors in flies. Such a neuropeptide circuit largely overlaps with the fruitless-expressing neural circuit that governs most aspects of male sexual behaviors. Thus DSK/CCKLR signaling in the sex circuitry functions antagonistically with P1 neurons to balance arousal levels and modulate sexual behaviors.

Highlights

Animals perform or terminate particular behaviors by integrating external cues and internal states through neural circuits
We speculated that neuropeptides might function as molecular modulators in courtship circuit to control courtship behaviors, Four pairs of Dsk and fruM neurons inhibit male courtship
We activated DskGAL4 neurons using dTrpA1 (Supplementary Fig. 5b) or CsChrimson (Supplementary Fig. 5c) in females and observed significantly reduced receptivity to courting wild-type males. These results indicate that Dskexpressing neurons are common in both sexes and suppress male and female sexual behaviors, and we focused on male courtship in this study

Summary

Introduction

Animals perform or terminate particular behaviors by integrating external cues and internal states through neural circuits. Substantial progress has been made into how external sensory cues are perceived and integrated by fruM and/or dsxM neurons to initiate male courtship, in particular, how a subset of male-specific fruM- and dsxM-expressing P1 neurons integrate olfactory and gustatory cues from female or male targets to initiate or terminate courtship[22,23,24,25,26]. Such a neuronal pathway is conserved in other Drosophila species[27,28,29]. We identify the neuropeptide Drosulfakinin (DSK), the fly ortholog of Cholecystokinin (CCK)

Methods

Results

Conclusion