Our hypothesis is that sleep influences on breathing result partially from regional activity changes in ventral medullary surface (VMS) areas which participate in chemoreceptor afferent processing, alter blood pressure influences on breathing, and change facilitatory influences on other respiratory regions. The regional alterations in VMS activity may result from changes in descending supramedullary influences, which are enhanced or reduced by different sleep states. We will test these possibilities in intact animals by 1) relating respiratory changes during different sleep- waking states to """"""""spontaneous"""""""" activity on VMS sites and in the paraventricular hypothalamus, which projects to the medullary surface; 2) applying resistive breathing, hypercapnic, hypoxic, peripheral chemoreceptor stimulation by cyanide, and blood pressure challenges during states, and mapping resulting VMS surface and hypothalamic activity while charting respiratory and cardiovascular responses; and 3) electrically stimulating hypothalamic regions during different states, and examining resultant influences on the VMS and on respiratory musculature and cardiovasculature activity. Microelectrodes and optical imaging probes will be placed in the paraventricular hypothalamus and on VMS areas that have a demonstrated potential to modify respiration or blood pressure, and thus may mediate state-related respiratory and cardiovascular effects. Single cell discharge, together with images of scattered 660 and 415 nm light (to measure activity by membrane movement and perfusion) will be collected during baseline and challenges within each sleep and waking state. Correlations of overall and regional changes in scattered light to upper airway and diaphragmatic respiratory muscle and cardiovascular patterns will be calculated using analog cross correlation, frequency- domain and event-related potential measures for optical recordings, and point-process techniques for cell discharge.
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