CARDIORESPIRATORY PATTERNS DURING SLEEP AND SIDS RISK

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The objective is to examine the mechanisms by which rostral brain areas affect respiratory control during sleep in the developing animal so that mechanisms of respiratory failure can be understood in victims of the sudden infant death syndrome (SIDS). We suggest that state influences modify descending input from rostral brain regions to specific respiratory areas of the midbrain and medulla, and place the developing organism at risk for obstructive sleep apnea by differentially enhancing diaphragmatic over upper airway action. We further suggest that the extent of influence from rostral areas changes with development. A newly described limbic arousal system that project to the nucleus of the solitary tract, parabrachial pons, and periaqueductal gray may underlie a large component of arousal-mediated upper airway muscle activation, and we plan to examine contributions to respiratory patterns at 3 ages in the kitten. The role of rostral structures in respiratory development will be studied by 1) examining "spontaneous" neuronal activity in particular regions of the ventral forebrain, midbrain, and medulla during sleep and waking, and relating this activity to upper airway nad diaphragmatic patterning, and 2) evoking activity in rostral regions and examining the resultant influence on neuronal activity in respiratory brainstem regions and on respiratory activity. Micro- and microelectrodes will be placed in rostral regions that have a demonstrated effect on respiratory patterning in the waking state and subserve functions altered by different states, and thus may be a component of the respiratory stimulus of "wakefulness." Neuronal discharge and slow-wave activity will be recorded in rostral hypothalamic regions implicated in temperature control, hippocampal regions related to motor patterning, and the central nucleus of the amygdala, an area implicated in "affective" arousal. We will record neurons in midbrain projection sites of these regions, the caudal lateral periaqueductal gray (which projects to premotor cells of facial, genioglossal, laryngeal, and abdominal motoneurons), the nucleus parabrachiales, and the Kolliker-Fuse nuclei of the parabrachial pons, as well as in the retroambiguus nucleus of the medulla. Respiratory pattern dependencies will be determined from cross- correlations of cell discharge with aspects of patterning of the diaphragm, a laryngeal abductor ( the cricothyroid), and an upper airway dilator (the posterior cricoarytenoid); regression procedures will determine relationships with aspects of the respiratory cycle and with blood pressure, measured with an implanted catheter. Phase-plane plots will be used to assess nonlinear aspects of respiratory patterning and neuronal discharge. Evoked activity will include warming and cooling of the preoptic region to manipulate temperature "drive" to respiration during each sleep-waking state.