NEURONAL BASIS FOR CARDIORESPIRATORY INTEGRATION

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This proposal is the continuation of our efforts to understand the CNS circuitry responsible for coordinating respiratory and vasomotor outflows. The present study focuses on the pathway of the sympathetic reflex triggered by stimulation of carotid chemoreceptors (chemosympathetic reflex). The general goal of the study is to unravel the main CNS relays of this reflex and to characterize some of the transmitters involved. Our main hypothesis is that, under anesthesia, the bulbar pathway of the sympathetic chemoreflex is almost completely separate from that of the baroreflex until the level of the bulbospinal premotor neurons where algebraic summation of the two inputs occurs. Based on preliminary experiments, we also believe that these premotor neurons are located in the rostral ventrolateral medulla and the ponto medullary transitional zone (A5 noradrenergic cells) . We also hypothesize that the sympathetic chemoreflex is mediated via the pre-Botzinger area, a small nucleus of the medulla oblongata responsible for the generation of the respiratory rhythm. This network will be investigated with neurophysiological methods in the anesthetized rat and with a newly introduced neurohistological technique (neuronal expression of the protooncogene product c-fos) which allows the mapping of active CNS networks. These experiments should significantly clarify the central circuitry responsible for the sympathetic chemoreflex, a homeostatic mechanism of fundamental importance in regulating arterial pressure and regional blood flows.