The regulation of regional blood flows and cardiac output is closely coordinated with respiration to ensure proper oxygen and carbon dioxide exchange in all body organs in the face of variable energy demands. Neural cardiovascular and respiratory reflexes which play important regulatory roles during health, may also contribute to clinical disorders such as sleep apnea in the adult and central and obstructive apnea of the newborn and the sudden infant death syndrome. The neuronal basis of respiratory rhythm generation and central cardiovascular control are only partially understood and the central connections responsible for the integration of these two essential functions remain largely conjectural. For example, the central pathways responsible for the excitatory influence of the medullary respiratory generator on the sympathetic outflow are totally unknown as are the intramedullary pathways responsible for the vasomotor effects produced by activation of cardioplumonary and other receptors which also control respiration. Much evidence already suggests that the rostral ventrolateral medulla may play a crucial role in cardiorespiratory integration and central chemosensitivity. Thus a major portion of the proposed research will be devoted to a study of several types of ventrolateral medullary cells which will be extensively characterized from the standpoint of connectivity, neurotransmitter content and electrophysiological properties. Efforts will be mainly concentrated on four rostral ventrolateral medullary reticulospinal cells, the C1 adrenergic neurons, neurons of nucleus interfascicularis hypoglossi, the Boetzinger complex expiratory related neurons and the sympathoexcitatory pace- maker neurons previously described in this laboratory. The experimental approach will include modern track-tracing techniques and single-unit recordings with iontophoretic application of drugs """"""""in vivo"""""""" and """"""""in vitro"""""""". Other experiments are also designed to test the hypothesis that certain types of bulbospinal respiratory premotorneurons located outside the rostral ventrolateral medulla might directly innervate spinal preganglionic neurons. In combination, these experiments will increase our understanding of the way in which central cardio- respiratory integration operates and may lead to the idenification of neurons with an essential role in central chemosensory function.
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