Physiological Genomics and Sex Differences of Central Vasopressin and Serotonin Circuits

项目摘要 社会行为与人类健康密不可分。我们关系的质量和性质， 社会互动影响情绪和焦虑，可以防止情绪困扰或导致情绪， 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， 许多疾病的病因和患病率也是如此。符合NIMH的使命， 了解包括社会行为在内的复杂行为的生物学基础， 科学家发展奖支持旨在确定基本单位，基因和细胞， 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老鼠身上进行的解剖工作发现， 加压素（AVP），一种神经肽递质，神经元到脑区，包括背侧 中缝，神经元产生血清素的地方。AVP和血清素系统之间的解剖学联系可能 形成一个渠道，通过它社会刺激/互动可以影响情绪和焦虑。第一步， 为了证明这些系统之间的功能联系，鲁德博士使用了电生理技术， 发现AVP激活5-羟色胺神经元，但间接地通过位于大脑中的局部回路神经元， 背缝本研究的目的是：1）确定中缝背核中的局部回路神经元， 以前未研究的细胞群; 2）表征神经元兴奋性的电特性， 雄性和雌性中AVP反应神经元和5-羟色胺神经元的离散亚群;以及3） 描绘性别特异性转录组（即，基因表达的完全互补）。 候选人Rood博士在行为神经科学方面接受过广泛的培训（来自纽约大学的博士学位）。 马萨诸塞州）和细胞生理学（在费城儿童医院进行博士后培训）。建筑 在强大的研究背景下，Rood博士将接受基因组学和小鼠遗传学方面的新培训， Susan Dymecki博士在哈佛医学院（HMS）的指导。其他培训包括 统计学和生物信息学课程，以及与各系教师的一对一指导 遗传学和神经生物学。HMS提供了一个世界一流的研究环境， 有必要对行为的基本机制进行前沿研究。除了top- 一流的教师，HMS环境提供了许多研讨会，近30个不同的核心设施，支持 生物学研究，最先进的实验室，和研究生的多元化社区， 博士后研究员在多个主题上进行研究。研究战略、培训和 环境联合收割机，以创造一个理想的途径，以满足博士鲁德的职业目标，成为一个独立的 顶尖研究机构的研究员

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.