Identification of a Site Critical to the Avpr1b's Effects on Behavior

描述（由申请人提供）：加压素1b受体一直被认为是调节社会行为的关键因素；然而，大脑中抗利尿激素1b受体起作用的确切区域尚未确定。本应用的目的是在实验动物模型中确定抗利尿激素通过抗利尿激素1b受体作用于其上的神经基质，从而影响社会行为。具体来说，所提出的实验旨在验证抗利尿激素1b受体介导的信号传导，特别是在海马的CA2区域内，有助于正常的社会行为表现的中心假设。这些研究的基本原理是，确定抗利尿激素通过抗利尿激素1b受体影响社会行为的神经解剖学基础，将有可能进一步加深我们对异常社会行为的理解。这一知识与NIH的使命相关，因为它将潜在地为人类精神疾病治疗提供新的靶点。该提议的具体目的是确定海马体CA2区域内抗利尿激素1b受体对社会行为的贡献。这将通过将实验动物行为研究与有针对性的、特定位点的基因敲除结合起来，以确定对行为调节重要的途径来实现。预计本研究的完成将有助于确定抗利尿激素1b受体调节社会行为的重要神经底物之一。这项研究具有重要意义，因为这项工作的发现将为更集中地研究抗利尿激素和其他神经递质系统之间的相互作用奠定基础；最终导致对社会行为调节的更全面的理解。拟议的研究很重要，因为它们有可能确定可能导致异常社会行为表现的关键神经基质之一。拟议的研究与公共卫生有关，因为行为调节的神经化学物质、神经基质和回路在进化上是保守的。因此，预计这些发现最终将适用于人类的健康。

DESCRIPTION (provided by applicant): The vasopressin 1b receptor has been consistently implicated as a key factor in the regulation of social behavior; however, the precise region of the brain where the vasopressin 1b receptor is acting has not been identified. The objective in this application is to identify neural substrates on which vasopressin acts via the vasopressin 1b receptor to affect social behavior in an experimental animal model. Specifically, the proposed experiments have been designed to test the central hypothesis that vasopressin 1b receptor mediated-signaling, specifically within the CA2 region of the hippocampus, contributes to normal displays of social behavior. The rationale for these studies is that identification of the neuroanatomical substrate upon which vasopressin acts via the vasopressin 1b receptor to impact social behavior will potentially further our understanding of aberrant social behavior. This knowledge is relevant to the NIH's mission in that it will potentially provide new targets for psychiatric disease treatment in humans. The specific aim of this proposal is to determine the contribution of the vasopressin 1b receptor within the CA2 region of the hippocampus to social behavior. This will be achieved by coupling experimental animal behavioral studies with targeted, site-specific, gene knockdown to identify pathways important to the regulation of behavior. It is expected that completion of this research will lead to the identification of one of the important neural substrates contributing to the vasopressin 1b receptor's regulation of social behavior. The proposed research is significant because the findings of this work will serve as a foundation for a more focused examination of the interaction between vasopressin and other neurotransmitter systems; ultimately resulting in a more complete understanding of the regulation of social behavior. PUBLIC HEALTH RELEVANCE The proposed studies are important because they have the potential to identify one of the key neural substrates that likely contributes to manifestations of aberrant social behavior. The proposed research has relevance to public health, because the neurochemicals, neurosubstrates, and circuits that underlying the regulation of behavior are evolutionarily conserved. Thus, the findings are ultimately expected to be applicable to the health of human beings.