Physiological Genomics and Sex Differences of Central Vasopressin and Serotonin Circuits

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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.