A considerable body of evidence indicates that behavioral and emotional factors may play an important role in cardiovascular disease, but the central nervous system mechanisms underlying this influence are poorly understood. The goal of the proposed project is to investigate the neuroanatomical, physiological and biochemical organization of the parabrachial nucleus, a cell group which appears to be a crucial link between the forebrain and brainstem areas involved in cardiovascular control. In the first series of experiments, the subnuclear organization of the afferent connections of the parabrachial nucleus will be studied in the rat, using antero-grade and retrograde axonal transport methods. In the second series of experiments, the neurotransmitter specificity of parabrachial subnuclei and their connections will be studied using immunohistochemical staining for enkephalin, somatostatin, cholecystokinin, corticotropin releasing factor, neurotensin and substance P and catecholamine synthetic enzymes (tyrosine hydroxylase and phenylethanolamine N-methyltransferase). In the third series of experiments, the potential neurotransmitters in specific parabrachial connections will be studied in the rat, using combined retrograde fluorescent tracers and immunofluorescence with the same antisera used in series two. In the fourth series of experiments, the responses of single parabrachial neurons in the rat to cardiovascular and other visceral stimuli will be recorded; when a cardiovascular-responsive neuron is found, a small iontophoretic deposit of either an anterograde or retrograde tracer will be made. The area will then be stimulated electrically, and cardiovascular and other visceral responses recorded. Finally, the correlation of pathways labeled in these brains with various potential neurotransmitters will be studied, by combining the tracer methods with immunohistochemistry. In the fifth series of experiments, similar though abbreviated studies will be done in cats and monkeys. Finally, the cytoarchitectonic and immunohistochemical organization of the parabrachial nucleus in the human brain will be studied. These experiments should give us some insight into the mechanisms of forebrain influence on cardiovascular control, in a variety of mammalian species up to, and including, man. The results may, eventually, allow the design of rational therapies at the central nervous system level for myocardial ischemia and cardiac arrhythmias.
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