College of Physics Science and Technology, Hebei University, Baoding 071002, China.
Key Laboratory of Digital Medical Engineering of Hebei Province, Hebei University, Baoding 071002, China.
Comput Math Methods Med. 2020 Sep 15;2020:8750167. doi: 10.1155/2020/8750167. eCollection 2020.
Gamma-aminobutyric acid (GABA) is critical for proper neural network function and can activate astrocytes to induce neuronal excitability; however, the mechanism by which astrocytes transform inhibitory signaling to excitatory enhancement remains unclear. Computational modeling can be a powerful tool to provide further understanding of how GABA-activated astrocytes modulate neuronal excitation. In the present study, we implemented a biophysical neuronal network model to investigate the effects of astrocytes on excitatory pre- and postsynaptic terminals following exposure to increasing concentrations of external GABA. The model completely describes the effects of GABA on astrocytes and excitatory presynaptic terminals within the framework of glutamatergic gliotransmission according to neurophysiological findings. Utilizing this model, our results show that astrocytes can rapidly respond to incoming GABA by inducing Ca oscillations and subsequent gliotransmitter glutamate release. Elevation in GABA concentrations not only naturally decreases neuronal spikes but also enhances astrocytic glutamate release, which leads to an increase in astrocyte-mediated presynaptic release and postsynaptic slow inward currents. Neuronal excitation induced by GABA-activated astrocytes partly counteracts the inhibitory effect of GABA. Overall, the model helps to increase knowledge regarding the involvement of astrocytes in neuronal regulation using simulated bath perfusion of GABA, which may be useful for exploring the effects of GABA-type antiepileptic drugs.
γ-氨基丁酸（GABA）对神经网络功能的正常运作至关重要，它可以激活星形胶质细胞以诱导神经元兴奋；然而，星形胶质细胞将抑制性信号转化为兴奋性增强的机制尚不清楚。计算建模可以是提供进一步了解 GABA 激活的星形胶质细胞如何调节神经元兴奋的有力工具。在本研究中，我们实施了一个生物物理神经元网络模型，以研究在暴露于递增浓度的外部 GABA 后，星形胶质细胞对兴奋性突触前和突触后末梢的影响。该模型根据神经生理学发现，在谷氨酸能神经胶质传递的框架内，完全描述了 GABA 对星形胶质细胞和兴奋性突触前末梢的影响。利用该模型，我们的研究结果表明，星形胶质细胞可以通过诱导 Ca 振荡和随后的神经递质谷氨酸释放来快速响应传入的 GABA。GABA 浓度的升高不仅自然地降低神经元的尖峰，而且增强星形胶质细胞的谷氨酸释放，导致星形胶质细胞介导的突触前释放和突触后缓慢内向电流增加。GABA 激活的星形胶质细胞诱导的神经元兴奋部分抵消了 GABA 的抑制作用。总的来说，该模型有助于增加关于星形胶质细胞在神经元调节中的参与的知识，使用模拟的 GABA 浴灌流，这可能有助于探索 GABA 型抗癫痫药物的作用。
