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.
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