HYPOTHALAMIC CONTROL OF THE CARDIORESPIRATORY SYSTEM

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The long-term goal of research in this laboratory is to elucidate the role of caudal hypothalamic neurons in regulating cardiorespiratory activity. The specific aims are to: 1) provide evidence for the physiological function of caudal hypothalamic neurons; 2) identify stimuli which alter the discharge of identified neurons; 3) determine projections of caudal hypothalamic neurons to lower brainstem and spinal cord sites; and 4) examine possible contributions of caudal hypothalamic neurons to elevated pressure present in spontaneously hypertensive rats. Both in vivo and in vitro preparations will be used to address these aims. The first set of experiments will be performed in anesthetized cats. Computer signal averaging techniques will be utilized to correlate basal discharge frequency of hypothalamic neurons with the cardiac cycle, sympathetic nerve activity and/or phrenic nerve activity. In addition, single unit responses of these neurons to various stimuli (hypoxia, hypercapnia, baroreceptor activation, pulmonary stretch receptor stimulation) will be recorded. An attempt will then be made to determine the axonal projection of all neurons studied using antidromic activation and mapping techniques. An in vitro rat brain slice preparation will be utilized to evaluate the direct effects of hypoxia and hypercapnia upon caudal hypothalamic neurons. Whole cell patch recordings will be performed in the brain slice experiments; retrograde transport of rhodamine microbeads will be used in an attempt to determine projection sites of studied neurons. In vivo experiments will also be undertaken in spontaneously hypertensive rats (SHR) to determine if neuronal activity in the caudal hypothalamus is altered relative to that of normotensive rats. Computer averaging techniques will determine the proportion of caudal hypothalamic neurons which have a cardiac and/or sympathetic discharge. Each neuron will also be tested for a response to baroreceptor stimulation. In a final set of experiments, characteristics of hypothalamic neurons from SHR rats will be compared to those of normotensive rats in a brain slice preparation. Comparisons will be made between neurons from young and mature spontaneously hypertensive rats and with normotensive controls. The results of these studies may offer insight into neurological abnormalities contributing to the origination and/or maintenance of high blood pressure and altered cardiorespiratory reflexes.