The Experimental Neurogenic Hypertension Program is a multidisciplinary research program investigating the neurobiology of central neural systems governing arterial pressure (AP). The broad objectives of the proposal are:(a) To identify and characterize, by electrophysiological and anatomical methods, the organization of arterial baro- and chemoreceptor reflexes in brainstem, in particular with respect to newly discovered functional areas of medulla, and to define the stimulus for the potent sympathoexcitation elicited by cerebral ischemia; (b) To establish, by physiological and ultrastructural methods, the pathways, transmitters, and hemodynamic, cellular, and molecular mechanisms responsible for the global elevations in cerebral cortical blood flow elicited by electrical stimulation of brain stem; (c) To define, by tracer methodology, the organization, connectivity, and biochemical anatomy of neurons in the medulla oblongata involved in autonomic regulation, particularly with respect to organization of the lateral tegmental field, the ventral medulla, and the interaction with structures of upper brainstem and thalamus; (d) To define, by EM-immunocytochemistry, the cellular basis for the synaptic interactions of chemically defined descending projection of ventral medulla with preganglionic sympathetic neurons in spinal cord and intramedullary connections between rostral and caudal ventrolateral medullary autonomic system (e) To asses. by EM-immunocytochemistry and in-situ hybridization methods, the cellular basis for the synaptic interaction within the nucleus tractus solitarii (NTS) of primary visceral afferents with opioid, catecholaminergic, and NPY and other peptidergic neuronal groups, and to define the ultrastructure and synaptic interactions in circumventricular organs; (f) To characterize functionally, in periphery and brain, the role of different subclasses of receptors for NPY, their interactions with other neurotransmitters (notably 1-glutamate in the NTS), the signal transduction mechanisms for each, and to isolate and clone each receptor class by heterologous expression in xenopus oocytes, by CDNA transfection, by PCR-generation of receptor candidates, and by DNA-mediated gene transfer.
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