This is an application for an Independent Scientist Award (K02) that would fundamentally enable the PI to devote at least 75 percent of his effort to research and career development. The PI's research has focused on animal models of processive stress to begin to trace and identify the neural circuits that mediate the activation of a specific stress responsive system, the hypothalamo-pituitary-adrenocortical (HPA) axis, and test the generality of the involvement of such a circuit across a variety of processive stressors. This work has been supported by a NARSAD Young Investigator Award, an NIMH B/START (R03 MH062471) award, and these studies will now be pursued through the recent award of a 5-year R01 (MH65327). This funded research provides the basis for the proposed Research Plan that examines in detail 1) which brain regions are specifically activated by exposure to two different processive stressors: audiogenic and predator odor stress; 2) whether any of the brain regions specifically activated by noise and predator odor project directly to the """"""""motor"""""""" neurons (paraventricular nucleus of the hypothalamus) of the HPA axis, and will include tests of functional relevance by ablating the cell bodies of these projecting neurons; and 3) the basic neurochemical phenotypes of the cellular groups that project directly to the paraventricular hypothalamic nucleus and are necessary for HPA axis activation in response to processive stress. The PI's immediate objectives are to expand and facilitate his current research on the basic neural circuits that elaborate a central state of stress, which in the longer-term might provide insights into putative dysregulation within these circuits that may be responsible for the development or precipitation of a number of mood and anxiety disorders. The Career Development Plan targets several technical (neuroanatomical tracing and single cell expression profiling techniques) and conceptual (concept of """"""""stress"""""""" and animal models of mood and anxiety disorders) areas of growth that will be achieved by enhanced scientific interactions, collaborations, and training, and will thus be vital in the attainment of the PI's short- and long-term career objectives. This will be done in an Institutional Environment with strong and continuing support to the PI's success via the provision of extensive laboratory space, physical resources, and accelerated growth of Neuroscience on campus. Through the Department approved teaching reduction, this award is unique in allowing the PI to devote a significantly greater amount of time and uninterrupted blocks of time to his research and career development, thereby assuring the success of the proposed growth initiatives.
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