PHYSIOLOGY AND PHARMACOLOGY OF CARDIOVASCULAR NEURONS

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Recent developments in electrophysiological and anatomical techniques have provided the opportunity to examine the central neural components of the reflex loops involved in regulating neural outflow to the heart and blood vessels. The first part of the work proposed here is a continuation of an electrophysiological and immunocytochemical study focusing on the medullary cells in the medial nucleus of the solitary tract (mNTS) that are involved in integrating information from the arterial baroreceptors and other peripheral and central sources. The studies focus on the mNTS neurons that are directly innervated by baroreceptor afferent fibers. The second part of the work begins a detailed examination of the properties of the baroreceptor neurons (the presynaptic neurons) that carry the arterial pressure information to the mNTS (the postsynaptic neurons). Recent progress has permitted anatomical identification of both groups of cells, those that transmit and those that receive the aortic baroreceptor innervation. Rats and guinea pigs are used as the animal models. The first aim is to assess the role of the six voltage dependent ionic currents that underlie spontaneous activity in the mNTS neuron that receives baroreceptor input and to determine the ability of this cell to transmit action potentials to the next neurons in the baroreflex pathway. This study, utilizing the nystatin pipette technique for voltage and/or current recording builds on data obtained in the previous granting period. The second aim continues a study of the transmitters responsible for excitatory and inhibitory modulation of mNTS activity. To complement our previous studies on glutamate and GABA we have targeted several potential transmitters based on our immunocytochemical studies of the region of the mNTS innervated by the left aortic depressor nerve. The third aim will pursue the proposal that presynaptic modulation of transmitter release from baroreceptor fibers occurs in response to the catecholamines, AII, somatostatin, CGRP substance P, and/or GABA. The action of these transmitters on the electrical activity of the aortic baroreceptor neurons will be explored.