The objective of these studies is to examine forebrain influences on respiratory and cardiovascular activity as a function of sleep- waking state. Specific protocols include long-term recording of single neurons in the ventral forebrain, pons, and medulla; cold blockade of these forebrain and pontine structures; temperature manipulation of thermosensitive hypothalamic areas; and intracellular examination of membrane potentials in lumbar sympathetic neurons. Neuronal discharge in ventral forebrain areas will be studied in relation to timing and degree of activation of diaphragmatic and upper airway muscles as well as cardiovascular parameters. Cardiovascular relationships to be studied include neuronal discharge correlations with 1) changes in cardiac cycle rate and variability associated with sleep states and 2) spontaneous and evoked blood pressure changes within states. Membane potential changes in lumbar sympathetic montoneurons will be examined during each sleep state, and following stimulation of medullary """"""""premotor"""""""" neurons. These studies will primarily use intact, drug-free cats, but decerebrate preparations in carbachol-induced atonia will be used for certain intracellular recordings. For recording of neurons during sleep and waking states, microelectrodes will be placed in the bed nucleus of the stria terminalis and central nucleus of the amygdala of the forebrain, and in brainstem areas associated with respiratory and cardiac control, including the hypoglossal, ambigus, solitary tract, and parabrachial pontine nuclei. Electrodes will be inserted for recording diaphragmatic, genioalossal, and laryngeal dilator muscle activity. Catheters will be positioned for recording venous and arterial pressure. Experimental variables include 1) different sleep-waking states, 2) transient elevation and lowering of blood pressure by means of phenylephrine and sodium nitroprusside administration and aortic balloon inflation, 3) hypercapnic and hypoxic challenges in intact and vagal-blocked preparations, and 4) electrical stimulation of forebrain and pontine sites. Cross-correlation procedures, nerve net detection, and selective analysis of internetwork versus intranetwork spike dependencies will be used to demonstrate discharge relationships between forebrain and brainstem areas. Neuronal discharge and respiratory muscle dependencies will be examined using pre-post stimulus time histograms and time series techniques.
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