Rybak I A, O'Connor R, Ross A, Shevtsova N A, Nuding S C, Segers L S, Shannon R, Dick T E, Dunin-Barkowski W L, Orem J M, Solomon I C, Morris K F, Lindsey B G
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
J Neurophysiol. 2008 Oct;100(4):1770-99. doi: 10.1152/jn.90416.2008. Epub 2008 Jul 23.
A large body of data suggests that the pontine respiratory group (PRG) is involved in respiratory phase-switching and the reconfiguration of the brain stem respiratory network. However, connectivity between the PRG and ventral respiratory column (VRC) in computational models has been largely ad hoc. We developed a network model with PRG-VRC connectivity inferred from coordinated in vivo experiments. Neurons were modeled in the "integrate-and-fire" style; some neurons had pacemaker properties derived from the model of Breen et al. We recapitulated earlier modeling results, including reproduction of activity profiles of different respiratory neurons and motor outputs, and their changes under different conditions (vagotomy, pontine lesions, etc.). The model also reproduced characteristic changes in neuronal and motor patterns observed in vivo during fictive cough and during hypoxia in non-rapid eye movement sleep. Our simulations suggested possible mechanisms for respiratory pattern reorganization during these behaviors. The model predicted that network- and pacemaker-generated rhythms could be co-expressed during the transition from gasping to eupnea, producing a combined "burst-ramp" pattern of phrenic discharges. To test this prediction, phrenic activity and multiple single neuron spike trains were monitored in vagotomized, decerebrate, immobilized, thoracotomized, and artificially ventilated cats during hypoxia and recovery. In most experiments, phrenic discharge patterns during recovery from hypoxia were similar to those predicted by the model. We conclude that under certain conditions, e.g., during recovery from severe brain hypoxia, components of a distributed network activity present during eupnea can be co-expressed with gasp patterns generated by a distinct, functionally "simplified" mechanism.
大量数据表明，脑桥呼吸组（PRG）参与呼吸相转换以及脑干呼吸网络的重构。然而，在计算模型中，PRG与腹侧呼吸柱（VRC）之间的连接在很大程度上是临时设定的。我们开发了一种网络模型，其PRG-VRC连接是根据体内协同实验推断得出的。神经元采用“整合-发放”方式进行建模；一些神经元具有源自Breen等人模型的起搏器特性。我们重现了早期的建模结果，包括不同呼吸神经元的活动概况和运动输出的再现，以及它们在不同条件下（迷走神经切断、脑桥损伤等）的变化。该模型还重现了在虚拟咳嗽和非快速眼动睡眠低氧期间体内观察到的神经元和运动模式的特征性变化。我们的模拟提出了这些行为期间呼吸模式重组的可能机制。该模型预测，在从喘息过渡到平稳呼吸的过程中，网络和起搏器产生的节律可能会共同表达，产生膈神经放电的组合“爆发-斜坡”模式。为了验证这一预测，在低氧和恢复过程中，对迷走神经切断、去大脑、固定、开胸和人工通气的猫的膈神经活动和多个单神经元放电序列进行了监测。在大多数实验中，低氧恢复期间的膈神经放电模式与模型预测的相似。我们得出结论，在某些条件下，例如在严重脑缺氧恢复期间，平稳呼吸时存在的分布式网络活动成分可以与由一种独特的、功能上“简化”的机制产生的喘息模式共同表达。
