The long term objectives of this project is to gain insight into how information emanating from respiratory afferents is integrated in the central nervous system and used to modulate respiration. Experiments planned represent a natural progression from our original proposal in year 1 of the program which focused on the ability of diaphragm afferents to modulate the respiratory motor output. the hypothesis to be tested in the present application is that the cerebellum (fastigial nucleus in particular) serves as s significant central integrative site for phrenic as well as other respiratory afferents in the reflex modulation of respiratory output. Ongoing studies utilizing the anesthetized, decerebellate preparation have demonstrated rather convincingly that the cerebellum contributes to the general reflex responses elicited by both mechanical and chemical respiratory challenges. Additional experiments are planned to: evaluate the involvement of the cerebellum and its deep nuclei in the modulation of reflex responses to activation of specific respiratory inputs (vagus, phrenic, intercostal, abdominal, carotid bodies, and central chemoreceptors); determine the effect of activating either cell bodies and/or fibers of passage within particular cerebellar nuclei on the firing behavior of meduallary respiratory-related neurons and correlate unit firing behavior with concomitant changes in the phrenic motor output; investigate the role of the pontine respiratory group and the Botzinger Complex in the cerebellar modulation of the phrenic motor output; and, characterize the response of individual respiratory-related cerebellar neurons to electrical, mechanical and chemical activation of respiratory inputs. The results should contribute to our understanding of respiratory regulation during eupneic and stressed breathing in normal and pathological conditions.
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