Our hypotheses are that the substantial variation in breathing and blood pressure that occurs in rapid eye movement (REM) sleep results partially from state-induced activity changes on regions within the ventral medullary surface (VMS), and that recovery from extreme changes in blood pressure or sustained apnea within sleep depends on the cerebellar fastigial nucleus and one of its afferent structures, the inferior olive. In intact cats, we will 1) identify sites within cerebellar and other brain areas activated by chemoreceptor and blood pressure challenges, and the sequence of activation, using functional magnetic resonance imaging; 2) relate spontaneous respiratory and blood pressure changes during sleep-waking states to VMS regional activity, and activity in the cerebellar fastigial nuclei and inferior olive; 3) apply chemoreceptor and blood pressure challenges during sleep-waking states, and assess fastigial nucleus and inferior olive activity while charting respiratory and cardiovascular responses; 4) electrically stimulate the fastigial nucleus, and examine state-related influences on the VMS and on respiratory and cardiovascular activity; and 5) examine regional activity patterns over the entire VMS unilaterally with respect to ventilatory and blood pressure challenges during different states. Blood oxygen level dependent Echo-Planar functional magnetic resonance images will be obtained using a high-field animal scanner during blood pressure, chemoreceptor, and saline control challenges with anesthetized cats. Baseline and challenge images will be compared on a voxel-by-voxel basis, using t tests with multiple-comparisons correction. Microelectrode and optical probes will be placed in the fastigial nucleus and inferior olive, and a large-array optical probe will be placed over the entire VMS unilaterally. Single cell discharge, and images of scattered 660 and 560 nm light (to measure activity and perfusion, respectively) will be collected during baseline, ventilatory, and pressor challenges within each sleep-waking state. Correlations of regional VMS activity changes to respiratory and cardiovascular patterns will be assessed using cross-correlation, frequency-domain and event-related potential measures for optical signals, and point-process techniques for cell discharge.
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