NEURAL MECHANISMS OF APNEA

虽然新生儿的呼吸调节有许多相似之处， 成年人之间存在着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 自发性呼吸暂停 长期目标是开发一个 了解影响稳定性的中枢神经机制 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。 三大研究 将进行：1）在体内细胞内记录 呼吸相关神经元 2)形态学鉴定 在早期发育过程中的特定细胞类型和3） 抑制性反射对脊髓神经元的仔猪。 已经开发了新生动物模型（猪），其中中央神经元（CNS）和中枢神经系统（CNS）均被激活。 通过测量间接评估神经呼吸功能 的膈神经活动，并直接通过细胞内 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， 在这些细胞中。 最后，高频振荡 膈神经的HFO将与吸气相关联。 HFO在各种呼吸相关神经元的突触突起中的作用。 第三个实验的目的是确定 这些振荡作为中央发展的标志， 呼吸中枢 本提案的第二项研究利用了 细胞内注射辣根过氧化物酶来描述 生理上鉴定的呼吸道发育形态 背侧和腹侧呼吸神经元。 最后一 一项研究调查了外周反射引起 延长呼吸抑制和个体呼吸 相关神经元接受单突触抑制或兴奋 输入。 中枢和外周抑制性和兴奋性的相互作用 对呼吸神经元中枢网络的影响是 对维持呼吸至关重要。 发展这一 相互作用对早产儿有重要意义， 有缺氧性脑损伤风险的呼吸暂停者， 有患婴儿猝死综合症的风险， 以及患有阻塞性睡眠呼吸暂停和其他异常的成年人， 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.