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SoSexOT - Deciphering Oxytocin Circuitries Orchestrating Socio-Sexual Behavior

SoSexOT - 解读协调社会性行为的催产素电路

基本信息

批准号：
316694078
负责人：
Professor Dr. Valery Grinevich
金额：
--
依托单位：
Institut des Neurosciences Cellulaires et Intégratives (INCI)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/316694078?language=en
关键词：
SoSexOT Deciphering Oxytocin Circuitries Orchestrating

项目摘要

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.

生殖是生物体的基本特征，在脊椎动物中主要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（SS）行为来实现的，这些行为在机制上可以分为前生殖行为和交配行为，两者都受到OT的调节。然而，OT效应背后的精确OT回路还远不清楚。虽然OT促进性行为是毫无疑问的，但OT回路通过前脑区域协调前冲动行为在很大程度上是未知的。为了解决这些问题，我们将采用最近开发的遗传技术（称为“基于病毒的遗传活性诱导的标记”，简称为vGAIT），只标记那些OT神经元，这些神经元在precopulatory和交配行为的大鼠被激活。使用这种技术，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预测，以及识别结构接收来自前脑，脑干和脊髓中标记的OT神经元的输入。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行为期间的特性和兴奋性。基于解剖学数据，我们将刺激轴突OT释放的前脑结构，功能与SS行为。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。预期的数据将是完全新颖的，并将提供机械的洞察到OT系统的生理SS行为的背景下。我们的建议与人类健康高度相关，因为它将为性唤起和生殖功能出现问题的患者的发病机制和可能的药物干预提供基础。