Structurally defined signaling in neuro-glia units in the enteric nervous system

Structurally defined signaling in neuro-glia units in the enteric nervous system
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DOI:
10.1002/glia.23596
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发表时间:
2019-06-01
期刊:
影响因子:
6.2
通讯作者:
Vanden Berghe, Pieter
Vanden Berghe, Pieter
中科院分区:
医学1区
文献类型:
--
作者:
Boesmans, Werend;Hao, Marlene M.;Vanden Berghe, Pieter

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胃肠功能的协调依赖于肠道神经元和神经胶质的共同作用,它们之间的相互作用对其活动的整合至关重要。为了研究肠神经节内肠神经元与神经胶质之间的信号传导机制,并描述其空间特征,我们开发了一种方法,在刺激单个肠神经元的同时监测邻近肠胶质细胞的活动。我们将单个肠神经元的胞质钙溶出与表达遗传编码钙指示剂的肠胶质细胞的钙成像结合起来,证明了肠神经元通过旁分泌嘌呤能途径通过泛内联蛋白向肠胶质细胞发出信号。对肠神经元的稀疏标记和对神经元细胞体、静脉曲张释放位点和肠胶质细胞之间结构关系的高分辨率分析发现,这种形式的神经元-胶质通讯存在于肠神经元细胞体与其周围的肠胶质细胞之间。我们的研究结果揭示了神经胶质单位作为肠神经系统中一个可操作的细胞组合的空间和功能基础。
Coordination of gastrointestinal function relies on joint efforts of enteric neurons and glia, whose crosstalk is vital for the integration of their activity. To investigate the signaling mechanisms and to delineate the spatial aspects of enteric neuron-to-glia communication within enteric ganglia we developed a method to stimulate single enteric neurons while monitoring the activity of neighboring enteric glial cells. We combined cytosolic calcium uncaging of individual enteric neurons with calcium imaging of enteric glial cells expressing a genetically encoded calcium indicator and demonstrate that enteric neurons signal to enteric glial cells through pannexins using paracrine purinergic pathways. Sparse labeling of enteric neurons and high-resolution analysis of the structural relation between neuronal cell bodies, varicose release sites and enteric glia uncovered that this form of neuron-to-glia communication is contained between the cell body of an enteric neuron and its surrounding enteric glial cells. Our results reveal the spatial and functional foundation of neuro-glia units as an operational cellular assembly in the enteric nervous system.