Elucidating the molecular and neural structure of female sexual reward

项目摘要 交配对繁殖是必不可少的，它深刻地影响着动物的生理、行为和福祉， 尤其是在女性身上。将交配经历与价态联系起来--要么是对积极刺激的胃口， 或者是消极的厌恶--允许雌性调整它们的交配策略并表现出适当的行为 在随后的相遇中的回应。然而，分配、储存、检索和 雌性的更新交配价在很大程度上是未知的。 我将用果蝇来询问性刺激的价值是如何分配和表达的 作为一种模范系统。我已经确定了一条神经通路(PLM通路)，它传递 交配对大脑的机械感觉，交配时肌肉抑制肽被释放。 有趣的是，PLM途径对于形成野生型的交配价态是必需的；因此，PLM途径 提供了一个极好的切入点来探索交配价是如何形成和维持的。我们已经产生了 积累了无与伦比的遗传工具来可视化和操纵这些神经元，我有 建立了新的行为范式来评估雌性果蝇的交配价。 在拟议的研究中，我的目标是描绘出构成这一代的分子和细胞底物。 交配价在雌性中的表达。我还将探索一种正交体验--社交 经验--调节雌性的交配价位。为了实现这些目标，我将进行三个方面的补充 利用多学科方法和前沿工具在分子遗传学、解剖学、 生理和行为。首先，我们将确定连接PLM神经元的分子和细胞通路 与苍蝇的初级学习中心合作，在那里分配价位。接下来，通过利用识别出的候选基因 在处女和交配雌性的转录组比较中，我将阐明分子和细胞机制。 这就是PLM通路神经元的戏剧性形态变化可能改变雌性交配潜伏期的基础。 最后，我将确定苍蝇应激反应途径中传递病理性社会暴露的基因 调节雌性的交配行为。总而言之，这些结果将极大地促进我们对 支持雌性交配价产生和调节的分子和神经通路。

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.