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胶质细胞-神经元相互作用是向全身性癫痫发作状态转变的基础。

Glia-neuron interactions underlie state transitions to generalized seizures.

机构信息

Faculty of Medicine and Health Sciences, Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, 7030, Trondheim, Norway.

Neuro-Electronics Research Flanders, 3001, Leuven, Belgium.

出版信息

Nat Commun. 2019 Aug 23;10(1):3830. doi: 10.1038/s41467-019-11739-z.

DOI:10.1038/s41467-019-11739-z
PMID:31444362
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6707163/
Abstract

Brain activity and connectivity alter drastically during epileptic seizures. The brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state. It is, however, less clear which mechanisms underlie the state transitions. By studying neural and glial activity in zebrafish models of epileptic seizures, we observe striking differences between these networks. During the preictal period, neurons display a small increase in synchronous activity only locally, while the gap-junction-coupled glial network was highly active and strongly synchronized across large distances. The transition from a preictal state to a generalized seizure leads to an abrupt increase in neural activity and connectivity, which is accompanied by a strong alteration in glia-neuron interactions and a massive increase in extracellular glutamate. Optogenetic activation of glia excites nearby neurons through the action of glutamate and gap junctions, emphasizing a potential role for glia-glia and glia-neuron connections in the generation of epileptic seizures.

摘要

在癫痫发作期间,大脑活动和连接会发生剧烈变化。大脑网络从平衡的静息状态转变为过度活跃和超同步状态。然而,哪些机制导致了状态的转变还不太清楚。通过研究癫痫发作的斑马鱼模型中的神经和神经胶质活动,我们观察到这些网络之间存在显著差异。在发作前期,神经元仅在局部显示出同步活动的小幅度增加,而缝隙连接耦联的神经胶质网络则在远距离高度活跃且高度同步。从发作前期状态到全身性癫痫发作的转变导致神经元活动和连接的突然增加,伴随着神经胶质-神经元相互作用的强烈改变和细胞外谷氨酸的大量增加。通过谷氨酸和缝隙连接的作用,光遗传学激活神经胶质会兴奋附近的神经元,强调神经胶质-神经胶质和神经胶质-神经元连接在癫痫发作中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/1e22e95fe3f8/41467_2019_11739_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/96c8d0a0f060/41467_2019_11739_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/a3146e4d5e4c/41467_2019_11739_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/94f655ca3875/41467_2019_11739_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/9734f79d46c7/41467_2019_11739_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/d16355eb1c63/41467_2019_11739_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/1e22e95fe3f8/41467_2019_11739_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/96c8d0a0f060/41467_2019_11739_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/a3146e4d5e4c/41467_2019_11739_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/94f655ca3875/41467_2019_11739_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/9734f79d46c7/41467_2019_11739_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/d16355eb1c63/41467_2019_11739_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/6707163/1e22e95fe3f8/41467_2019_11739_Fig6_HTML.jpg

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