Physiological Genomics and Sex Differences of Central Vasopressin and Serotonin Circuits

项目摘要 社会行为与人类健康有着千丝万缕的联系。我们关系的质量和性质，以及 社会互动会影响情绪和焦虑，并可以防止情绪困扰或导致情绪和 焦虑症以及攻击性增加。此外，男性和女性之间的社会行为往往不同。 许多疾病的病因和流行率也是如此。契合NIMH更好的使命 理解包括社会行为在内的复杂行为的生物学基础，这项指导研究 科学家发展奖支持旨在识别基本单位、基因和细胞的研究 调节社会行为并提供高通量基因表达谱训练的神经回路 候选人本杰明·鲁德博士。鲁德博士在小鼠身上进行的解剖学研究发现了轴突 加压素(AVP)是一种神经肽递质，神经元向包括背部在内的脑区投射 中缝，神经元产生5-羟色胺的地方。AVP和5-羟色胺系统之间的解剖联系可能 形成一个渠道，通过这个渠道，社会刺激/互动可以影响情绪和焦虑。在第一步中 为了证明这些系统之间的功能联系，罗德博士使用了电生理学技术 发现AVP激活5-羟色胺神经元，但间接地通过位于 背侧中缝。该方案的研究目标是：1)确定中缝背侧的局部环路神经元 以前未被研究的细胞群；2)表征神经兴奋性潜在的电特性 男性和女性AVP反应神经元和5-羟色胺神经元的离散亚群； 描述这些神经元群体的性别特异性转录组(即，基因表达的完全互补)。 候选人鲁德博士接受过广泛的行为神经科学培训(加州大学博士学位 马萨诸塞州)和细胞生理学(费城儿童医院博士后培训)。建房 在强大的研究背景下，Rood博士将在以下方面接受新的基因组学和老鼠遗传学培训 哈佛医学院(HMS)苏珊·迪梅基博士的指导。其他培训包括 统计学和生物信息学的课程工作以及与以下系教员的一对一指导 遗传学和神经生物学。HMS提供世界一流的研究环境，拥有所有的资源 有必要对行为的基本机制进行前沿研究。除了TOP- 一流的教职员工，HMS环境提供无数的研讨会，近30个不同的核心设施支持 生物研究，最先进的实验室，以及多样化的研究生和 博士后研究员对许多主题进行研究。研究策略、培训和 环境的结合创造了一条理想的道路，以满足路德博士成为独立医生的职业目标 一家顶级研究机构的调查员。

Project Summary Social behavior and human health are inextricably linked. The quality and nature of our relationships and social interactions affect mood and anxiety and can protect against emotional distress or lead to mood and anxiety disorders as well as increased aggression. Further, social behavior often differs between men and women as does the etiology and prevalence of many disorders. Fitting with the mission of the NIMH to better understand the biological basis of complex behavior including social behavior, this Mentored Research Scientist Development Award supports research designed to identify the fundamental units, genes and cells, of neural circuits that modulate social behavior and provides training in high throughput gene expression profiling for the candidate, Dr. Benjamin Rood. Anatomical work in mice conducted by Dr. Rood identified axonal projections of vasopressin (AVP), a neuropeptide transmitter, neurons to brain areas including the dorsal raphe, where neurons produce serotonin. The anatomical link between AVP and the serotonin system may form a conduit through which social stimuli / interactions can impact mood and anxiety. In a first step in demonstrating a functional connection between these systems, Dr. Rood used electrophysiological techniques to discover that AVP activates serotonin neurons, but indirectly through a local circuit neuron located in the dorsal raphe. Research goals of this proposal are to 1) identify the local circuit neuron in the dorsal raphe, a previously unstudied cell population; 2) characterize the electrical properties underlying neuronal excitability in discrete subpopulations of AVP-responsive neurons and serotonin neurons in both males and females; and 3) profile the sex-specific transcriptome (i.e., full complement of gene expression) of these neuronal populations. The candidate, Dr. Rood, is broadly trained in behavioral neuroscience (PhD from the University of Massachusetts) and cell physiology (postdoctoral training at the Children's Hospital of Philadelphia). Building on a strong research background, Dr. Rood will undergo new training in genomics and mouse genetics under the mentorship of Dr. Susan Dymecki at Harvard Medical School (HMS). Additional training includes coursework in statistics and bioinformatics and one-on-one mentoring with faculty in the Departments of Genetics and Neurobiology. HMS provides a world-class research environment with the all the resources necessary to carry out cutting-edge research on the fundamental mechanisms of behavior. In addition to top- notch faculty, the HMS environment offers numerous seminars, nearly 30 different core facilities supporting biological research, state-of-the-art laboratories, and a diverse community of graduate students and postdoctoral fellows carrying out research on a multitude of topics. The research strategy, training, and environment combine to create an ideal pathway to meet Dr. Rood's career goal of becoming an independent investigator at a top research institution.