Development of genetic tools to study central Avp1b receptors

描述(申请人提供)：在人类中，有证据表明神经肽加压素可能在以异常社交行为为特征的精神健康障碍的发展和/或严重程度中发挥作用，如精神分裂症和自闭症谱系障碍。这个R03应用程序的目标是开发用于探索 加压素1b受体在行为丰富的物种中的作用，其中已知加压素对社会行为的神经调节很重要，特别是叙利亚仓鼠和草原田鼠。拟议的实验旨在检验中心假设，即在哺乳动物物种中，后叶加压素1b受体在序列、分布和功能上是保守的。这一知识与NIMH的使命相关，因为它将促进我们对以异常社会行为为特征的精神障碍背后的神经化学的了解。提出了一个特定的目标，旨在确定加压素1b受体在叙利亚仓鼠和草原田鼠中的序列和分布，并开发用于未来功能研究的遗传工具。这项拟议的研究意义重大，因为通过确定加压素1b系统的保守程度以及它如何调节社会行为，可以提高我们对人类加压素系统的理解。 公共卫生相关性：拟议的研究很重要，因为它们将提供对两种模式生物中加压素系统的洞察，这两种模式生物具有丰富的社会行为，并对我们对人类加压素系统的了解做出了实质性贡献。这项拟议的研究与公共健康相关，因为许多神经化学物质、神经底物和神经行为调节回路在进化上是保守的。因此，这项工作的发现有望适用于人类的心理健康。

DESCRIPTION (provided by applicant): In humans, there is evidence that the neuropeptide vasopressin may play a role in the development and/or severity of mental health disorders characterized by aberrant social behavior, such as schizophrenia and autism spectrum disorders. The objective of this R03 application is to develop genetic tools for the exploration of the role of the vasopressin 1b receptor in species that are behaviorally rich and in which vasopressin is known to be important to the neural regulation of social behavior, specifically, Syrian hamsters and prairie voles. The proposed experiments have been designed to test the central hypothesis that across mammalian species the vasopressin 1b receptor is conserved in sequence, distribution, and function. This knowledge is relevant to the mission of the NIMH because it will further our knowledge of the neurochemistry underlying psychiatric disorders characterized by abnormal social behavior. One specific aim is proposed that is designed to determine the sequence and distribution of the vasopressin 1b receptor in Syrian hamsters and prairie voles, as well as to develop genetic tools to use in future functional studies. The proposed research is significant because by determining how conserved the vasopressin 1b system is and how it modulates social behavior and our understanding of the vasopressin system in humans can be improved. PUBLIC HEALTH RELEVANCE: The proposed studies are important because they will provide insight into the vasopressin system in two model organisms that have rich social behavior and have made substantial contributions to our knowledge of the vasopressin system in humans. The proposed research has relevance to public health because many of the neurochemicals, neurosubstrates, and circuits that the neural regulation of behavior are evolutionarily conserved. Thus, the findings of this work are expected to be applicable to the mental health of human beings.