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 for prolonged spontaneous apnea. The long range goal is to develop an understanding of central neural mechanisms that affect stability of respiratory drive. The major objective of the present proposal is the neurophysiologic characterization of specific medullary neurons which control breathing in newborns. Three main studies are to be performed: 1) in vivo intracellular recording of respiratory related neurons. 2) morphologic identification of specific cell types during early development and 3) effects of inhibitory reflexes on the medullary neurons of the piglet. A newborn animal model (swine) has been developed in which central neural respiratory function is assessed indirectly by measurement of the phrenic neural activity and directly by intracellular recording of medullary respiratory neural activity. The first study will investigate the effects of age on the biophysical properties of the medullary respiratory neurons. Further, synaptic inputs during the different stages of respiration will be characterized in these cells. Finally, high frequency oscillations (HFOs) of the phrenic nerve will be correlated with inspiratory HFOs in the synaptic nolse of various respiratory related neurons. The goal of this third experiment is to determine the mechanism of these oscillations as markers of development in central respiratory centers. The second study in this proposal utilizes intracellular injection of horseradish peroxidase to describe the developmental morphology of physiologically identified respiratory neurons in the dorsal and ventral respiratory groups. The last study investigates the mechanism by which peripheral reflexes cause prolonged respiratory inhibition and whether individual respiratory related neurons receive monosynaptic inhibitory or excitatory inputs. The interaction of central and peripheral inhibitory and excitatory influences on the central network of respiratory neurons is critical for maintenance of breathing. Development of this interaction has important implications for premature newborns with apnea who are at risk for hypoxic cerebral damage, older infants at risk for the Sudden Infant Death Syndrome, as well as infants and adults with obstructive sleep apnea and other anomalies of respiratory control.