ROLE OF NEUROCHEMICALS IN RESPIRATORY PATTERN FORMATION

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Breathing, and its adjustment during health and disease, is of fundamental physiological importance. There is now an extensive body of knowledge, largely derived from in situ leurophysiological experiments, concerning the organization of the central neuronal circuit which initiates and coordinates rhythmic breathing movements in mammals. The long-term goal of my research is too extend this knowledge to the cellular level, and define how the central respiratory circuit is assembled from a collection of anatomical, biophysical, and neurochemical building blocks. Currently, my laboratory is funded by a five year NIH grant (HL- 39929-01). Utilizing an in vitro brainstem slice preparation,, this project is directed towards defining the role of specific neurochemical and intrinsic membrane properties in sculpturing the activity of neurons located within the porsal respiratory group (DRG) of guinea pigs. The specific aims are to: (i) define glasses (and subclasses) of neurons in the region of the DRG possessing unique combinations of morphological, biophysical, and pharmacological properties, (ii) determine the mechanism(s) of action for these neurochemical, and (iii) identify sites within the DRG where multiple neurochemical actions might occur. Building upon the success of this in vitro approach, I have formulated a career development plan designed to enhance the resolution of my current research program and extend it to other elements of the central respiratory circuit in the future. The central theme of this development plan is to acquire expertise in whole cell/patch clamping and neuroanatomical staining techniques. To do this, a combination of training experience in laboratories successfully employing these technologies, continued interaction with members of the Respiratory Group at the University of Kentucky, and a total commitment to research and research related activities for the next five years is proposed. In support of these goals, the University of Kentucky has provided me with the additional equipment and space necessary to eventually implement these techniques in my own laboratory. The underlying premise, if this proposal is that to achieve full independence as an investigator, and attract quality graduate and post doctoral students, I must firmly establish my laboratory as a site where "state of the art" biophysical studies are done in association with the anatomical localization of respiratory neurons and neurotransmitters. The resources and environment available at the University of Kentucky, coupled with the career development plan outlined in this application, assures the realization of this goal.