Oxytocin Ligand/Receptor Variants and Social Behavior

项目总结/摘要 脑内神经肽催产素（OT）和精氨酸加压素（AVP）在改变神经元的功能中起重要作用。 调节社会行为的回路这些配体在许多领域调节规范的社会功能， 包括社会依恋、父母行为、攻击性和复杂的社会认知。病理 在大脑/行为条件下，许多障碍的特征在于社交领域的显著缺陷。 了解OT和AVP改变神经元细胞功能的方式有可能同时识别 产生社会功能障碍的机制，并设计使细胞功能正常化的化合物， 行为本项目利用了新的OT配体结构的发现，以及 绒猴是一种表现出社会性一夫一妻制的物种， 男性和类似家庭的社会结构。第一个目标将表征配体多样性对细胞的影响。 通过使用体内行为药理学改变各种社会领域的行为。These domains 包括男女依恋、照顾婴儿、配偶防御攻击和社会合作/利他主义。的 第二个目标是定量受体药理学和配体变体与 这些相关配体的细胞膜G蛋白偶联受体。最终目标将确定具体的 这些配体引起的G蛋白介导的细胞信号传导过程的改变，以确定 改变社会行为的配体变异是通过特异性或“偏向性”激活不同的 信号通路总的来说，这三个目标将为我们提供重要的见解， 神经元和行为被OT和AVP配体变体修饰，从而增强了对 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- 受体复合物可以作为治疗社会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.