The goal of this project is to define brain stem network mechanisms through which hypercapnia, carotid chemoreceptors, carotid baroreceptors, and cutaneous nociceptors shape the respiratory motor pattern. Multi-array recording technology, spike train analysis, and spike-triggered averaging of intracellular recordings will be used to measure the responses and functional associations of many neurons corded simultaneously in the medullary raphe nuclei, pontine respiratory group, and Botzinger-ventral respiratory group (BOT-VRG) of anesthetized or decerebrate artificially ventilated cats. Network models derived from these data will be tested with computer simulations. Planned experiments will address five hypotheses. Hypothesis 1; Pontine and medullary networks operate together to modulate the respiratory motor pattern in response to: a) brain stem hypercapnia (i.e., central chemoreception); b) carotid chemoreceptor stimulation, c) carotid baroreceptor stimulation, and d) cutaneous nociceptor stimulation. Hypothesis 2: Multiple reflex systems share pontomedullary networks in the regulation of the respiratory motor pattern. Hypothesis 3: Pontomedullary networks include internal checks and balances that regulate the duration and magnitude of carotid chemoreceptor and baroreceptor reflex actions on breathing. Hypothesis 4: Baroreceptor reflex actions in pontomedullary networks modulate nociceptive reflex actions on breathing. Hypothesis 5: Reflexively induced transient and long-term configurations of pontomedullary networks generate spatiotemporal patterns of synchrony, not apparent in conventional measures of firing rate, that act on the BOT-VRG. Improved treatments and management of disorders of respiratory and cardiovascular control depend on improved understanding of the neural system that regulates these functions. This project will complement advances currently being made with other in vivo and in vitro reductionistic approaches and identify network sites and processes where inherited or acquired abnormalities could disrupt breathing.
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