The objective is to test the hypothesis that failure in the sudden infant death syndrome (SIDS) results from a dysfunction during sleep of the ventral medullary surface (VMS), or in supramedullary projections to cardiac and respiratory areas of the VMS, thus altering the capability of this area to mediate blood pressure changes which affect arousal and respiratory patterning. SIDS victims show signs suggestive of a """"""""failure to arouse,"""""""" diminished variation in cardiac and respiratory intervals indicative of impaired respiratory-cardiovascular interactions, and evidence indicating diminished muscarinic binding on the VMS. Dysfunctional areas within the VMS, or in projections to this surface area, would place infants at risk during respiratory and cardiovascular challenges in sleep. The role of regional VMS areas in mediating ventilatory and pressor challenges will be examined during sleep-waking states at four ages in kittens by l) assessing """"""""spontaneous"""""""" activity during sleep-waking states in VMS regions, using single cell discharge, evoked potential, and optical imaging techniques; 2) evaluating regional VMS responses to graded hypoxic, hypercapnic, loaded breathing and cyanide challenges, and pressor and depressor manipulations; 3) relating VMS activity evoked by challenges to patterns of upper airway and diaphragmatic activity, and to blood pressure; 4) stimulating supramedullary regions, and examining the resultant influence on VMS sites and on cardiorespiratory activity. A coherent image fiber optic probe and camera will be placed on the VMS, together with a moveable bundle of microelectrodes under sterile surgery. Stimulation electrodes will be placed in supramedullary regions that have demonstrated projections to the VMS, or show pronounced activation to respiratory challenges. EMG patterning of the diaphragm and a laryngeal abductor and dilator (cricothyroid and posterior cricoarytenoid, respectively), will be used for respiratory measures. Images of reflected light changes associated with neural activity, including vascular and cell swelling changes, will be digitized, together with single cell discharge and wide- band activity from attached microelectrodes during undisturbed sleep states, and during cardiorespiratory challenges within states. Time series analysis, using spectral, coherence and lagged correlation techniques, will be used to relate overall and regional VMS activity changes across conditions to the respiratory and cardiac cycle and to blood pressure variation.
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