SoSexOT - Deciphering Oxytocin Circuitries Orchestrating Socio-Sexual Behavior

生殖是生物体的一个基本特征，在脊椎动物中很大程度上受下丘脑神经肽催产素(OT)及其同系物的调节。在哺乳动物中，生殖功能是通过复杂的社会性行为来实现的，这些行为可以机械地分为交配前行为和交配行为，两者都受到OT的调节。然而，加班效应背后的精确加班电路还远不清楚。尽管OT促进性行为是毋庸置疑的，但通过前脑区域协调交配前行为的OT回路在很大程度上是未知的。为了解决这些问题，我们将使用一种最近发展起来的遗传技术(称为基于病毒的遗传活动诱导标记，缩写为vGAIT)来仅标记在大鼠交配前和交配行为中激活的OT神经元。利用这项技术，我们将阐明这种OT神经元在下丘脑的空间分布、它们的表型和它们的投射，以及识别从标记的OT神经元在前脑、脑干和脊髓接受输入的结构。同时，在自由活动的大鼠中，我们将记录这些OT神经元的活动，以阐明它们在SS行为中的特性和兴奋性。基于解剖学数据，我们将刺激与SS行为相关的前脑结构中轴突OT的释放。最后，使用光遗传学和药物遗传学技术，我们将激活或抑制标记的OT神经元的整个群体，以监测SS行为的变化。预期的数据将是全新的，并将在SS行为的背景下提供对OT系统的生理学的机械性见解。我们的建议与人类健康高度相关，因为它将为性唤醒和生殖功能出现问题的患者提供发病机制和可能的药物干预的基础。

Reproduction is an essential feature of living organisms and is largely modulated in vertebrates by hypothalamic neuropeptide oxytocin (OT) and its homologs. In mammals, reproductive function is realized by complex socio-sexual (SS) behaviors, which can be mechanistically divided into precopulatory and copulatory behaviors, both modulated by OT. However, precise OT circuits underlying OT effects are far from clear. Although there are no doubts that OT promotes sexual behavior, the OT circuits orchestrating precopulatory behavior via forebrain regions are largely unknown. To address these questions, we will employ a recently developed genetic technique (called 'virus-based Genetic Activity-Induced Tagging' and abbreviated as vGAIT) to tag only those OT neurons which were activated during precopulatory and copulatory behaviors of rats. Using this technique, we will elucidate spatial distribution of such OT neurons in the hypothalamus, their phenotype and their projections as well as identify structures receiving input from tagged OT neurons in the forebrain, brainstem, and spinal cord. In parallel, in freely moving rats, we will record the activity of these OT neurons to elucidate their properties and excitability during SS behavior. Based on anatomical data, we will stimulate axonal OT release in those forebrain structures which are functionally related with SS behavior. At the end, using optogenetic and pharmacogenetic techniques, we will activate or inhibit entire populations of tagged OT neurons to monitor changes in SS behavior. The expected data will be entirely novel and will provide mechanistic insights into the physiology of the OT system in the context of SS behavior. Our proposal is highly relevant to human health as it will provide a basis for pathogenesis and possible pharmacological intervention in patients experiencing problems with sexual arousal and reproductive function.