BIOGENIC AMINE SYSTEMS, CRF, AND STRESS

描述(申请者摘要)：这是一份针对高级科学家的建议 由研究科学家资助的研究人员颁发的奖项(K05) 过去10年的发展奖(K02)。之前的K02资金推动了 通过提供时间开发新方法和促进生产力来促进PI的职业生涯 合作。在研究层面上，这导致了从单一到 美国国立卫生研究院资助的3个主要相关研究项目。在技术层面上， 专业技术从主要在体内的电生理方法发展到 包括体内微透析，以及复杂的系统和细胞 神经解剖学技术。在职业层面，私家侦探成立了一个部门， 精神病学系的应激神经生物学[在Hahnemann 大学]。年2月，该司迁至#年儿童医院。 在费城，PI被提供了一个著名的斯托克斯队职位 宾夕法尼亚大学的研究员和教员职位。这个 拟议的研究计划整合了3个资助的研究计划的各个方面，以 解决全球假设促肾上腺皮质激素释放因子的影响 生物胺系统在急性应激反应中是不可或缺的， 这些相互作用的应力诱导可塑性是某些 与压力相关的精神病理学。拟议的职业发展计划将使 PI将开发新的细胞方法并将其纳入实验 目前用于阐明CRF-生物胺的系统方法 应力诱导塑性的相互作用和机制。这些措施包括 体外切片中的细胞和分子电生理技术 重组病毒载体的制备及对CRF基因表达的调控 特定的CRF传入生物胺核团。这些技术将武装 PI具有一系列必要的工具，以解决关于多个 级别(从蜂窝到系统)。职业发展的第二个方面是 动员CHOP/UPenn社区内的基础和临床研究人员 在压力神经生物学中心分享对压力的共同兴趣。 电子通信、定期研究研讨会、静修和分享 公共资源用于促进以下方面的互动和协作 教职员工。因为该中心将重点研究压力作为致病因素， 它不是针对特定疾病的，而是一种理想的治疗机制 了解和开发针对不同医学和行为的新治疗方法 精神错乱。与之前的K02奖一样，K05奖将促进未来 通过提供稳定的工资支持和灵活性来实现职业发展 增强技术技能和概念基础，提升领导力。

DESCRIPTION (applicant's abstract): This is a proposal for a Senior Scientist Award (K05) from an investigator who has been funded by a Research Scientist Development Award (K02) for the last 10 years. Prior K02 funding advanced the PI's career by providing time to develop new approaches and foster productive collaborations. At a research level this resulted in expansion from a single to 3 major interrelated NIH-funded research programs. At a technical level, expertise went from predominantly in vivo electrophysiological approaches to including in vivo microdialysis, as well as sophisticated systems and cellular neuroanatomical techniques. At a career level, the PI established a Division of Stress Neurobiology within the Department of Psychiatry [at Hahnemann University]. In February the Division moved to the Children's Hospital of Philadelphia where the PI was offered a prestigious position as a Stokes Investigator and faculty position at the University of Pennsylvania. The proposed research plan integrates aspects of the 3 funded research programs to address the global hypothesis that the impact of corticotropin-releasing factor on biogenic amine systems is integral in the acute stress response and that stress-induced plasticity of these interactions underlies certain stress-related psychopathology. The proposed career development plan will allow the PI to develop and incorporate new cellular approaches into the experimental repertoire of systems approaches currently used to elucidate CRF-biogenic amine interactions and mechanisms underlying stress-induced plasticity. These include cellular and molecular electrophysiological techniques in in vitro slice preparations and the use of viral vectors to manipulate CRF expression in specific CRF afferents to biogenic amine nuclei. These techniques will arm the PI with a range of tools necessary to address research questions on multiple levels (from cellular to systems). A second aspect of career development is to mobilize basic and clinical investigators within the CHOP/ Upenn community who share a common interest in stress in a Center for Stress Neurobiology. Electronic communications, regular research seminars, retreats and shared common resources are used to foster interactions and collaborations among faculty. Because the Center will focus on stress as an etiological factor, rather than on a specific disease, it promises to be an ideal mechanism for understanding and developing new treatments for diverse medical and behavioral disorders. Like the previous K02 award, the K05 award will promote future career development by providing stable salary support and flexibility to enhance technical skills and conceptual bases and promoting leadership.