Sakamoto Ryuta, Kameno Rikiya, Kobayashi Taira, Ishiyama Asahi, Watanabe Kazuo, Hoshino Osamu
Department of Intelligent Systems Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki, 316-8511, Japan.
Southern Tohoku Research Institute for Neuroscience, Southern Tohoku General Hospital, 7-115, Yatsuyamada, Koriyama, Fukushima, 963-8563, Japan.
Biol Cybern. 2019 Jun;113(3):257-271. doi: 10.1007/s00422-019-00793-x. Epub 2019 Feb 12.
Until recently, glia, which exceeds the number of neurons, was considered to only have supportive roles in the central nervous system, providing homeostatic controls and metabolic supports. However, recent studies suggest that glia interacts with neurons and plays active roles in information processing within neuronal circuits. To elucidate how glia contributes to neuronal information processing, we simulated a sensory neuron-glia (neuron-astrocyte) network model. It was investigated in association with ambient (extracellular) GABA level, because the astrocyte has a major role in removing extracellular GABA molecules. In the network model, transporters, embedded in plasma membranes of astrocytes, modulated local ambient GABA levels by actively removing extracellular GABA molecules which persistently acted on receptors in membranes outside synapses and provided pyramidal cells with inhibitory currents. Gap-junction coupling between astrocytes mediated a concordant decrease in local ambient GABA levels, which solicited a prompt population response of pyramidal cells (i.e., activation of an ensemble of pyramidal cells) to a sensory stimulus. As a consequence, the reaction time of a motor network, to which axons of pyramidal cells of the sensory network project, to the sensory stimulus was shortened. We suggest that the astrocytic gap-junction coupling may assist in organizing dynamic cell assemblies by coordinating a reduction in local ambient GABA levels, thereby shortening reaction time to sensory stimulation.
直到最近,数量超过神经元的神经胶质细胞在中枢神经系统中还被认为仅具有支持作用,提供稳态控制和代谢支持。然而,最近的研究表明,神经胶质细胞与神经元相互作用,并在神经回路的信息处理中发挥积极作用。为了阐明神经胶质细胞如何促进神经元信息处理,我们模拟了一个感觉神经元 - 神经胶质细胞(神经元 - 星形胶质细胞)网络模型。该模型结合细胞外γ-氨基丁酸(GABA)水平进行研究,因为星形胶质细胞在清除细胞外GABA分子方面起主要作用。在网络模型中,嵌入星形胶质细胞质膜的转运体通过主动清除持续作用于突触外膜上受体并为锥体细胞提供抑制性电流的细胞外GABA分子,调节局部细胞外GABA水平。星形胶质细胞之间的缝隙连接耦合介导了局部细胞外GABA水平的一致降低,这引发了锥体细胞对感觉刺激的快速群体反应(即一组锥体细胞的激活)。结果,感觉网络的锥体细胞轴突投射到的运动网络对感觉刺激的反应时间缩短。我们认为,星形胶质细胞的缝隙连接耦合可能通过协调局部细胞外GABA水平的降低来协助组织动态细胞集合,从而缩短对感觉刺激的反应时间。