This is an application for an Independent Scientist Award (K02) that would be essential in allowing the PI to devote at least 75 percent of his effort to his research program and research career development. For the past 6 years the PI has systematically studied a stress habituation paradigm in rats and found that the expression of habituation depended on corticosteroid negative feedback, especially as a result of corticosteroid actions mediated by mineralocorticoid receptors (MR). This work was primarily supported by NIH B-Start (MH54742) and R29 (DK49143) awards. Recently, the PI has been awarded a 5-year R01 award (MH62456) to pursue further these studies. The funded research project entails an extensive range of studies that will 1) determine the brain regions critical to MR-mediated modulation of stress habituation, 2) characterization of CRH and AVP gene expression and modulation with habituation and altered corticosteroid negative feedback, 3) examination of the extent to which HPA axis stress habituation is associated with a generalized shift in MR-mediated corticosteroid negative feedback, and 4) determine if HPA axis stress habituation is associated with changes in corticosteroid receptor expression. The PI's immediate career objectives are to extend his research program in terms of its quality, productivity and breadth of technical expertise. The PI's long-term career objective is to make a substantial scientific contribution to the understanding of the neural adaptive processes that impact on stress responses. A Career Development Plan is proposed that will be instrumental in helping the PI achieve these career objectives by extending the PI's collaborations and training in the areas of neuroanatomy, cell biology, molecular biology, and systems physiology. Increased knowledge, technical expertise and interaction with specialists in each of these areas will be vital for ongoing and future studies in the PI's laboratory designed to decisively determine underlying mechanisms of stress adaptation. The PI's Department and Institution are committed to supporting the PI's research program and have provided extensive laboratory space and physical resources. Through Department approved teaching reduction, the K02 award will increase substantially the amount of time and coherent blocks of time that the PI can devote to his research and career development, thereby assuring the success of these endeavors.
