NEURAL MECHANISMS OF APNEA

尽管新生儿的呼吸调节有许多相似之处 对于成年人，存在数量和质量上的差异。它 这些发育差异可能解释了 新生儿对长时间的明显易感性 自发性呼吸暂停。长期目标是开发一种 对影响稳定性的中枢神经机制的理解 呼吸驱动。本提案的主要目标是 是特定延髓的神经生理学特征 控制新生儿呼吸的神经元。三项主要研究 要执行的是：1)体内细胞内记录 呼吸相关神经元。2)形态鉴定 早期发育中的特定细胞类型以及3) 仔猪延髓神经元的抑制性反射。 已经建立了一种新生动物模型(猪)，在该模型中， 通过测量间接评估神经呼吸功能 和直接通过细胞内的 记录延髓呼吸神经活动。第一 研究将调查年龄对生物物理的影响 延髓呼吸神经元的特性。此外，突触 在呼吸的不同阶段的输入将是 以这些细胞为特征。最后，高频振荡 膈神经(HFOS)与吸气相关 呼吸相关神经元突触内的HFO。 第三个实验的目标是确定 将这些振荡作为中环地区发展的标志 呼吸中心。该提案中的第二项研究利用 细胞内注射辣根过氧化物酶以描述 生理鉴定呼吸系统的发育形态 背侧呼吸组和腹侧呼吸组的神经元。最后 一项研究调查了外周反射引起的机制 持续的呼吸抑制和个体呼吸是否 相关神经元接受单突触抑制或兴奋 投入。 中枢和外周抑制与兴奋的相互作用 对呼吸神经元中枢网络的影响 对维持呼吸至关重要。这方面的发展 互动对早产儿有重要的影响 有缺氧性脑损伤风险的呼吸暂停者，年龄较大的婴儿 婴儿猝死综合症的风险，以及婴儿 以及患有阻塞性睡眠呼吸暂停和其他睡眠障碍的成年人 呼吸控制。

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.