The proposed project is a request for a K02 award for the applicant to develop skills now required by new results in a programmatic investigation of cytokine-to-brain communication. Extensive evidence indicates that cytokines are critically involved in immune-to-brain communication. Indeed, cytokine-to-brain communication is of central importance in an organism's ability to respond to and survive immunological challenge. Alterations in neural function produced by cytokines such as IL1-beta may also be important for understanding stress and stress-related disorders such as depression. The candidate and colleagues have recently demonstrated (a) IL-1 binding sites on paraganglia which form afferent synapses with subdiaphragmatic vagal afferents and (b) that severing the subdiaphragmatic vagus blocks a variety of IL1-beta mediated responses. These data suggest that vagal afferents may provide a key neural pathway for cytokine signaling to brain. The research development and professional growth goals of the proposal involve a vigorous continuing education program for the PI, consisting of a number of academic courses, short courses, and workshops, as well as specialized conferences. In addition, the PI will intensively train with experts there at the University of Colorado, Boulder. The training will focus on molecular biology, immunohistochemistry and retrograde tracing, and electrophysiology. Additionally, the released time will foster further professional growth by yielding coherent blocks of time for concentrating on research and review projects.
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