Oxytocin Ligand/Receptor Variants and Social Behavior

项目摘要/摘要 脑神经肽催产素(OT)和精氨酸加压素(AVP)在改变神经功能中起重要作用 调节社会行为的回路。这些配基在许多领域规范着社会职能， 包括社会依恋、父母行为、攻击性和复杂的社会认知。在病理上 在大脑/行为状况方面，许多障碍的特点是社交领域的严重缺陷。 了解催产素和精氨酸加压素改变神经元细胞功能的方式有可能识别 产生社会功能障碍的机制和设计使细胞功能正常化的化合物和 行为。本项目利用了新的OT配体结构的发现，以及在 绒猴体内OT和AVP的细胞受体，一种表现出社会一夫一妻制的物种，通过 男性，以及像家庭一样的社会结构。第一个目标将表征配体多样性对蛋白质的影响。 通过使用体内行为药理学改变不同社会领域的行为。这些域 包括男女依恋、婴儿护理、配偶防御攻击性和社会合作/利他主义。这个 第二个目标是量化受体药理学和配体变异体与 细胞膜G蛋白偶联受体为这些相关配体。最终目标将定义具体的 这些配体对G蛋白介导的细胞信号转导过程的修饰以确定 改变社会行为的配基变异是通过激活不同的 信号通路。总而言之，这三个目标将为以下方面提供重要的见解 神经元和行为被OT和AVP配体变体改变，导致对 社会行为的神经生物学。该项目可以指出设计神经肽配体的潜在选择- 受体复合体可以作为治疗社交功能障碍的有效工具。

Project Summary/Abstract The brain neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important roles in altering neural circuits that regulate social behavior. These ligands regulate normative social function in a host of areas, including social attachment, parental behavior, aggression, and complex social cognition. In pathological brain/behavior conditions, many disorders are characterized by dramatic deficits in the social realm. Knowledge of the way OT and AVP alter cellular function in neurons has the potential to both identify mechanisms that produce social dysfunction and to design compounds that normalize cellular function and behavior. The present project takes advantage of the discovery of novel OT ligand structure, and variation in cellular receptors for OT and AVP in the marmoset, a species that exhibits social monogamy, infant care by males, and a family-like social structure. The first aim will characterize the effects of ligand diversity on the alteration of behavior in a variety of social domains by using in vivo behavioral pharmacology. These domains include male-female attachment, infant care, mate-defense aggression, and social cooperation/altruism. The second aim will quantify the receptor pharmacology and binding characteristics of the ligand variants with the cell membrane G protein-coupled receptors for these related ligands. The final aim will define the specific modifications in G protein-mediated cell signaling processes brought about by these ligands to determine if ligand variation that modifies social behavior does so through specific or `biased' activation of different signaling pathways. Collectively, these three aims will provide important insights into the ways in which neurons and behavior are modified by OT and AVP ligand variants, leading to enhanced knowledge of the neurobiology of social behavior. The project can point to potential options for designing neuropeptide ligand- receptor complexes that could serve as effective tools to treat social dysfunction.