PHYSIOLOGY AND PHARMACOLOGY OF CARDIOVASCULAR NEURONS

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The long term goal of these studies addresses the mechanisms of the neural regulation of the cardiovascular system, in particular heart rate and arterial pressure. Recent developments in electrophysiological and anatomical techniques have provided the opportunity to examine the central neural components of the reflect loops involved in regulating neural outflow to the heart and blood vessels. The work proposed here is an electrophysiological and immunocytochemical study focusing on the cells of the medial arterial baroreceptors and other peripheral and central sources. The first aim is to examine the physiological role of six currents that have been identified and characterized in isolated mNTS neurons. These currents underlie spontaneous activity in the neuron and determine the ability of the cells to transmit action potentials to the next cells in the baroreflex pathway. This portion of the study will utilized conventional microelectrode voltage recording and specific channel blockers. Modulation of this area will then be studied as too will influence the activity of the baroreflex pathway. Two of these substances, glutamate and GABA, are released on the same call from synaptic boutons that are co-isolated with the neurons as remnants of the afferent innervation. This is the basis of the second aim which continues a study of the excitatory and inhibitory synaptic mechanisms responsible for spontaneous and stimulated transmitter release. Preliminary evidence suggesting presynaptic modulation of this release will also be pursued. The third aim will explore the response of the neurons to other potential transmitter substance including the catecholamines, serotonin and substance P. The fourth aim will be pursued concurrent with the other studies. The neurons that are characterized by electrical and transmitter responses will also be examined using immunocytochemical and fluorescence techniques at the light and electron microscopic level for the presence of potential transmitter substances in the soma and attached boutons. The results will provide information on the transmission across the baroreceptor reflex and what modulates it as well as providing basic information about the mechanism of central synaptic transmission.