Advances in the Study of Social Neuroendocrinology

项目摘要 神经精神疾病代表了广泛的复杂的情绪和行为障碍，但许多 这些都与适应不良的社会反应有关。不幸的是，我们没有足够清晰的 了解这些疾病背后的神经机制或它们共有的基本症状。 虽然已经变得清楚的是在神经回路中存在实质性的重叠（即，社会行为 神经网络）控制不同的社会和情感行为，研究行为如何的技术 从这样一个复杂的交互神经网络中涌现出来的方法一直缺乏。社会行为的变化， 跨物种和特定物种的个体内，至少部分来自遗传和表观遗传 社会行为神经网络中的差异，我们现在能够理解 调节这种变化的分子机制。这些遗传差异表现为 神经回路的关键分子元件如神经递质、受体、转运蛋白、生长因子 等目前在这一领域取得进展的一个重要限制是没有完善的基因组- 工程技术的一些最好的动物物种研究社会行为和组织。 在这些生物中，叙利亚仓鼠（Mesocricetus auratus）已被证明是一种 这是一种非常有用的啮齿动物模型，用于研究社会行为，并且有丰富的数据， 其中已经产生的PI，对神经生物学和激素机制控制社会 识别、社交回避、攻击和社交。该项目的目标是克服 通过在叙利亚开发和实施最先进的基因组工程技术， 仓鼠模型，使基因如何在神经回路中发挥作用的分子询问，以调节复杂的 社会行为为了实现这一目标，我们将利用基因组工程来产生转基因和基因- 有针对性的突变仓鼠，将用于研究基因的功能， 社会行为这些转基因和基因靶向仓鼠的产生将由我们的 最近生成的叙利亚仓鼠转录组数据，将用于专门针对和操纵 各种神经行为相关的仓鼠基因首先，作为原则证明，我们将重点关注 精氨酸-加压素V1 a受体，因为该受体在调节广泛的 独特的社会行为以及我们长期以来在研究该系统方面的专业知识。成功 为叙利亚仓鼠开发转基因和基因靶向方法将提供变革性工具 研究社区探索社会行为的神经遗传学基础。

Project Summary Neuropsychiatric illnesses represent a wide range of complex emotional and behavioral disorders, but many of these are associated with maladaptive social responses. Unfortunately, we do not have a clear enough understanding of the neural mechanisms underlying these disorders or the fundamental symptoms they share. While it has become clear that there is a substantial overlap in the neural circuitry (i.e., the Social Behavior Neural Network) controlling different social and emotional behaviors, the technology to study how behavior emerges from such a complex interacting neural network has been lacking. Variation in social behavior, both across species and within individuals of given species, arises at least in part from genetic and epigenetic differences within the Social Behavior Neural Network, and we are now in a position to understand the molecular mechanisms mediating this variation. These genetic differences are expressed as variations in critical molecular elements of neural circuits such as neurotransmitters, receptors, transporters, growth factors, etc. A significant current limitation to progress in this area is that there are no well-established genome- engineering technologies for some of the best animal species for studying social behavior and organization. Among these organisms are Syrian hamsters (Mesocricetus auratus), which have proven to be an exceptionally useful rodent model for the study of social behavior and for which there is a wealth of data, much of which has been generated by the PIs, on the neurobiological and hormonal mechanisms controlling social recognition, social avoidance, aggression, and social communication. The goal of this project is to overcome this limitation by developing and implementing state of the art genome engineering technologies in the Syrian hamster model to enable molecular interrogation of how genes act within neural circuits to regulate complex social behavior. To achieve this goal, we will use genome engineering to generate transgenic and gene- targeted mutant hamsters that will be used to investigate the function of genes that have been implicated in social behavior. The generation of these transgenic and gene-targeted hamsters will be facilitated by our recently generated Syrian hamster transcriptome data, which will be used to specifically target and manipulate a variety of neurobehaviorally-relevant hamster genes. Initially, as a proof of principle, we will focus on the arginine-vasopressin V1a receptor because of the significance of this receptor in regulating a wide range of distinct social behaviors and our long-demonstrated expertise with studying this system. The successful development of transgenic and gene-targeting approaches for Syrian hamsters will provide transformative tools to the research community for exploring the neurogenetic bases of social behaviors.