Corticosteroid Dependent Mechanisms of Stress Adaptation

描述(由申请人提供)：这是一份申请独立科学家奖(K02)的申请书，这将是允许PI将至少75%的精力投入到他的研究计划和研究职业发展中的关键。在过去的6年里，PI系统地研究了大鼠的应激习服范式，发现习服的表达依赖于皮质类固醇的负反馈，特别是由盐皮质激素受体(MR)介导的皮质类固醇作用的结果。这项工作主要由NIH B-Start(MH54742)和R29(DK49143)奖支持。最近，国际和平研究所获得了为期5年的R01奖(MH62456)，以继续进行这些研究。这项由基金资助的研究项目涉及广泛的研究，包括1)确定对MR介导的应激习服调节至关重要的大脑区域，2)CRH和AVP基因表达的特征以及习惯化和改变的皮质类固醇负反馈的调节，3)检查HPA轴应激习服与MR介导的皮质类固醇负反馈的普遍变化相关的程度，以及4)确定HPA轴应激习服是否与皮质类固醇受体表达的变化有关。PI的直接职业目标是从质量、生产率和技术专长的广度方面扩展他的研究计划。PI的长期职业目标是为理解影响应激反应的神经适应过程做出实质性的科学贡献。提出的职业发展计划将有助于通过扩大私人助理在神经解剖学、细胞生物学、分子生物学和系统生理学领域的合作和培训，帮助私人助理实现这些职业目标。增加这些领域中每一个领域的知识、技术专长和与专家的互动，对于PI实验室正在进行的和未来的研究至关重要，该实验室旨在决定性地确定压力适应的潜在机制。国际和平研究所的部门和研究所致力于支持国际和平研究所的研究计划，并提供了广泛的实验室空间和物理资源。通过部门批准的教学缩减，K02奖励将大大增加PI可用于研究和职业发展的时间和连贯的时间段，从而确保这些努力的成功。

DESCRIPTION (provided by applicant): 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.