Elucidating the molecular and neural structure of female sexual reward

项目摘要 交配对于生殖是必不可少的，它深刻地影响着动物的生理、行为和幸福， 尤其是女性。将交配经验与效价联系起来--要么是对积极刺激的欲望， 或厌恶的负面-允许女性调整他们的交配策略， 在随后的遭遇中做出反应。然而，分子和细胞基质分配，储存，检索， 雌性的最新交配价基本上是未知的。 我将用果蝇来研究性刺激的效价是如何分配和表达的 melanogaster，作为一个模型系统。我已经确定了一个神经通路（PLM通路）， 肌肉抑制肽是交配时释放到大脑的机械感觉。 有趣的是，PLM途径是发展交配的野生型效价所必需的;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。我们创造了， 我收集了一系列无与伦比的遗传工具来可视化和操纵这些神经元， 建立了新的行为模式来评估雌性果蝇的交配价。 在拟议的研究中，我的目标是描绘的分子和细胞基板的基础上产生的 以及雌性交配价的表达。我还将探讨一种正交的体验--社交 经验--调节雌性的交配价。为了实现这些目标，我将进行三个补充 利用分子遗传学，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 与果蝇的初级学习中心联系在一起，在那里效价被分配。接下来，通过利用候选基因识别 在转录组比较处女和交配的女性，我将阐明分子和细胞机制 这是PLM通路神经元的巨大形态变化的基础，可能会改变雌性交配潜伏期。 最后，我将在果蝇的压力反应途径中识别出基因，这些基因将病理性的社会暴露传递给 调节雌性的交配行为总之，这些结果将大大促进我们对 分子和神经通路的基础上产生和调节雌性的交配价。

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.