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体外自主呼吸和喘息发生时主导吸气性多神经元活动模式的构成和动力学。

Configuration and dynamics of dominant inspiratory multineuronal activity patterns during eupnea and gasping generation in vitro.

机构信息

Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Queretaro, Mexico.

出版信息

J Neurophysiol. 2021 Apr 1;125(4):1289-1306. doi: 10.1152/jn.00563.2020. Epub 2021 Jan 27.

DOI:10.1152/jn.00563.2020
PMID:33502956
Abstract

The pre-Bötzinger complex (preBötC), located within the ventral respiratory column, produces inspiratory bursts in varying degrees of synchronization/amplitude. This wide range of population burst patterns reflects the flexibility of the preBötC neurons, which is expressed in variations in the onset/offset times of their activations and their activity during the population bursts, with respiratory neurons exhibiting a large cycle-to-cycle timing jitter both at the population activity onset and at the population activity peak, suggesting that respiratory neurons are stochastically activated before and during the inspiratory bursts. However, it is still unknown whether this stochasticity is maintained while evaluating the coactivity of respiratory neuronal ensembles. Moreover, the preBötC topology also remains unknown. In this study, by simultaneously recording tens of preBötC neurons and using coactivation analysis during the inspiratory periods, we found that the preBötC has a scale-free configuration (mixture of not many highly connected nodes, hubs, with abundant poorly connected elements) exhibiting the rich-club phenomenon (hubs more likely interconnected with each other). PreBötC neurons also produce multineuronal activity patterns (MAPs) that are highly stable and change during the hypoxia-induced reconfiguration. Moreover, preBötC contains a coactivating core network shared by all its MAPs. Finally, we found a distinctive pattern of sequential coactivation of core network neurons at the beginning of the inspiratory periods, indicating that, when evaluated at the multicellular level, the coactivation of respiratory neurons seems not to be stochastic. By means of multielectrode recordings of preBötC neurons, we evaluated their configuration in normoxia and hypoxia, finding that the preBötC exhibits a scale-free configuration with a rich-club phenomenon. preBötC neurons produce multineuronal activity patterns that are highly stable but change during hypoxia. The preBötC contains a coactivating core network that exhibit a distinctive pattern of coactivation at the beginning of inspirations. These results reveal some network basis of inspiratory rhythm generation and its reconfiguration during hypoxia.

摘要

位于腹侧呼吸柱内的 Pre-Bötzinger 复合体(preBötC)产生不同同步/幅度的吸气爆发。这种广泛的群体爆发模式反映了 preBötC 神经元的灵活性,表现在它们的激活起始/结束时间以及在群体爆发期间的活动变化,呼吸神经元在群体活动起始和群体活动峰值时表现出较大的周期到周期时间抖动,表明呼吸神经元在吸气爆发之前和期间是随机激活的。然而,在评估呼吸神经元集合的共激活时,这种随机性是否仍然存在还不清楚。此外,preBötC 的拓扑结构也仍然未知。在这项研究中,通过同时记录数十个 preBötC 神经元并在吸气期间使用共激活分析,我们发现 preBötC 具有无标度配置(由少数高度连接的节点、枢纽组成,具有丰富的低度连接元素),表现出丰富俱乐部现象(枢纽更有可能相互连接)。PreBötC 神经元还产生高度稳定的多神经元活动模式(MAPs),并在缺氧诱导的重新配置期间发生变化。此外,preBötC 包含一个共享其所有 MAPs 的共激活核心网络。最后,我们发现吸气起始时核心网络神经元的顺序共激活存在独特模式,表明在多细胞水平上评估时,呼吸神经元的共激活似乎不是随机的。通过多电极记录 preBötC 神经元,我们在正常氧和缺氧条件下评估了它们的配置,发现 preBötC 具有无标度配置和丰富俱乐部现象。PreBötC 神经元产生高度稳定但在缺氧期间发生变化的多神经元活动模式。preBötC 包含一个共激活核心网络,在吸气开始时表现出独特的共激活模式。这些结果揭示了吸气节律产生及其在缺氧期间重新配置的一些网络基础。

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