NEURAL MECHANISMS OF APNEA

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Though respiratory regulation in newborns has many similarities with adults, quantitative and qualitative differences exist. It is possible that these developmental differences account for the pronounced susceptibility of newborn infants to have prolonged spontaneous apnea. The present studies are based on the hypothesis that central neural mechanisms are more important in respiratory regulation than traditionally recognized. The long-range goal is to develop an understanding of central neural mechanisms that destabilize respiratory drive. The specific objective of this study is to develop techniques and assure feasibility for projects using intracellular recording of brainstem respiratory neurones in developing animals. Intracellular recording of respiratory-related activity in different cell populations will be undertaken to determine cellular mechanisms which lead to prolonged post-stimulus respiratory effects. A model has been developed demonstrating that reflexes originating in the superior laryngeal nerve induce prolonged activity in post-inspiratory neurones. These neurones are prominently active during phase switching from inspiration to expiration. Therefore, prolonged activation of these neurones is a likely mechanism of apnea. Two studies are proposed to further characterize this mechanism. The first study is to investigate the mechanisms by which activation of post-inspiratory cells cause inspiratory neurone quiesence. Second, the means by which upper airway stimulation results in prolonged post-inspiratory activation will be determined. The second study is designed specifically to distinguish between 1) direct and indirect synaptic activation of post-inspiratory cells, and 2) whether prolonged post-stimulus neuronal activity is due to continued synaptic stimulation or membrane conductance changes. These two studies are to be accomplished in adult cats. The third portion of this project is to determine the feasibility of applying this technology to study of developmental aspects of central neuronal integration of respiratory activity. There does not currently exist an established model for this type of study. The above two studies performed at the Physiologisches Institut of the Universitat Heidelberg will provide the technical framework for application of similar studies in newborns to be performed during this project's second year. Central integration of inhibitory reflexes may have important implications for premature newborns with apnea, older infants at risk for the Sudden Infant Death Syndrome, as well as infants and adults with obstructive sleep apnea.