Vasopressin Receptors and Social Attachment

描述（由申请人提供）：本提案旨在支持候选人Larry J. Young博士的持续职业发展。杨博士是埃默里大学精神病学和行为科学系的副教授，也是行为神经科学中心（CBN）的教员。埃默里大学和CBN为候选人的研究计划的持续发展提供了理想的环境。杨博士的工作重点是复杂社会行为背后的分子、细胞和神经生物学机制。候选人的长期目标是采用最先进的技术来了解社会行为中个体差异的分子机制。候选人的研究使用高度社会化和一夫一妻制的草原田鼠作为动物模型，表明血管加压素受体（V1aR）在调节亲和行为中起着关键作用。分子研究表明，编码V1aR（avprla）的基因的变异有助于社会行为的个体变异。本提案中的目标旨在检验四个具体假设。第一个目标将测试的假设，在一个avprla微卫星多态性直接有助于变异V1aR分布在大脑中使用敲入小鼠的方法。第二个目标使用基于病毒载体的siRNA方法来直接测试avprla表达的变化有助于草原田鼠社会行为变化的假设。第三个目标中的研究将检验这一假设，即田鼠中avprla表达的多样性是使用选择性育种策略的社会行为中可遗传变异的主要来源。第四个目标将直接检验人类AVPR1A中的多态性有助于人类社会认知变化的假设。这些目标中的每一个都涉及到在候选人的研究计划中实施新的实验方法。职业发展计划将需要与埃默里大学和国外的同事合作，以发展候选人在使用同源重组创建敲入小鼠，使用siRNA技术调节基因表达，基因组学和人类遗传分析方面的专业知识。该提案中概述的研究对于理解与自闭症谱系障碍（ASD）相关的社会障碍的病因具有重要意义。最终，这些发现可能会导致新的治疗目标，用于治疗这种毁灭性疾病的特征社会障碍。

DESCRIPTION (provided by applicant): This proposal seeks support for the continued career development of the Candidate, Larry J. Young, PhD. Dr. Young is an Associate Professor in the Department of Psychiatry and Behavioral Sciences and a faculty member in the Center for Behavioral Neuroscience (CBN) at Emory University. Emory and the CBN provide an ideal environment for the continued development of the Candidate's research program. Dr. Young's work focuses on the molecular, cellular and neurobiological mechanisms underlying complex social behaviors. The long-term goal of the Candidate is to incorporate state-of-the-art technologies to understand the molecular mechanisms underlying individual variation in social behaviors. Using the highly social and monogamous prairie vole as an animal model, the Candidate's research suggests that the vasopressin receptor (V1aR) plays a critical role in modulating affiliative behaviors. Molecular studies suggest that variation in the gene encoding V1aR (avprla) contributes to individual variation in social behavior. The Aims in this proposal are designed to test four specific hypotheses. The first Aim will test the hypothesis that polymorphisms in an avprla microsatellite directly contribute to variation in V1aR distribution in the brain using a knock-in mouse approach. The second Aim uses a viral vector-based siRNA approach to directly test the hypothesis that variation in avprla expression contributes to variation in social behavior in prairie voles. Studies in the third Aim will test the hypothesis that diversity in avprla expression in the vole is a primary source of heritable variation in social behavior using a selective breeding strategy. The fourth Aim will directly test the hypothesis that polymorphisms in the human AVPR1A contribute to variation in human social cognition. Each of these Aims involves the implementation of new experimental approaches into the Candidate's research program. The Career Development Plan will entail collaborations with colleagues at Emory and abroad to develop the Candidate's expertise in creating knock-in mice using homologous recombination, modulating gene expression using siRNA technology, genomics and human genetic analyses. The research outlined in this proposal has important implications for understanding the etiology of the social impairments associated with Autism Spectrum Disorders (ASD). Ultimately, these findings may lead to novel therapeutic targets for the treatment of the social impairments which characterize this devastating disorder.