Elucidating the molecular and neural structure of female sexual reward

项目总结

Project Summary Mating is essential for procreation, and it profoundly affects animals’ physiology, behavior, and wellbeing, particularly in females. Associating mating experience with a valence––either appetitive for a positive stimulus, or aversive for negative––allows females to adjust their mating strategy and exhibit appropriate behavioral responses in subsequent encounters. Yet, the molecular and cellular substrates that assign, store, retrieve, and update mating valence in females are largely unknown. I will interrogate how the valence of sexual stimuli is assigned and expressed using the fruit fly, Drosophila melanogaster, as a model system. I have identified a neural pathway (PLM pathway) that conveys the mechanosensation of copulation to the brain, where Myoinhibitory peptide is released upon copulation. Intriguingly, the PLM pathway is required for to develop wild-type valence for mating; thus, the PLM pathway provides a superb entry point to explore how mating valence is formed and maintained. We have generated and amassed an unparalleled collection of genetic tools to visualize and manipulate these neurons, and I have established novel behavioral paradigms to evaluate mating valence in female Drosophila. In the proposed study, I aim to delineate the molecular and cellular substrates that underlie the generation and expression of mating valence in female. I will also explore how an orthogonal experience––social experience––regulates females’ mating valence. To achieve these goals, I will carry out three complementary projects that exploit multidisciplinary approaches and cutting-edge tools in molecular genetics, anatomy, physiology, and behavior. First, we will determine the molecular and cellular pathways that link PLM neurons with the fly’s primary learning centers, where valence is assigned. Next, by exploiting candidate genes identified in transcriptome comparison in virgin and mated females, I will elucidate the molecular and cellular mechanisms that underlie the dramatic morphological changes of PLM pathway neurons that likely alter female mating latency. Finally, I will identify genes in the fly’s stress-response pathway that convey pathological social exposure to modulate females’ mating behavior. Together, these results will substantially advance our understanding of the molecular and neural pathways that underpin the generation and regulation of females’ mating valence.