Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
Glia. 2019 Jun;67(6):1167-1178. doi: 10.1002/glia.23596. Epub 2019 Feb 7.
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.
胃肠道功能的协调依赖于肠神经元和神经胶质细胞的共同努力，它们之间的串扰对于整合它们的活动至关重要。为了研究信号机制，并描绘肠神经节内肠神经元与神经胶质细胞之间通讯的空间方面，我们开发了一种方法，即在监测相邻肠神经胶质细胞活性的同时刺激单个肠神经元。我们将单个肠神经元的细胞质钙离子释放与表达遗传编码钙指示剂的肠神经胶质细胞的钙成像相结合，并证明肠神经元通过缝隙连接蛋白通过旁分泌嘌呤能途径向肠神经胶质细胞发出信号。肠神经元的稀疏标记和神经元细胞体、曲张释放部位和肠神经胶质细胞之间结构关系的高分辨率分析表明，这种神经元-神经胶质细胞通讯形式存在于肠神经元的细胞体与其周围的肠神经胶质细胞之间。我们的结果揭示了神经胶质单元作为肠道神经系统中一个操作细胞组合的空间和功能基础。
