According to the tripartite synapse model, astrocytes have a modulatory effect on neuronal signal transmission. More recently, astrocyte malfunction has been associated with psychiatric diseases such as schizophrenia. Several hypotheses have been proposed on the pathological mechanisms of astrocytes in schizophrenia. For example, post-mortem examinations have revealed a reduced astrocytic density in patients with schizophrenia. Another hypothesis suggests that disease symptoms are linked to an abnormality of glutamate transmission, which is also regulated by astrocytes (glutamate hypothesis of schizophrenia). Electrophysiological findings indicate a dispute over whether the disorder causes an increase or a decrease in neuronal and astrocytic activity. Moreover, there is no consensus as to which molecular pathways and network mechanisms are altered in schizophrenia. Computational models can aid the process in finding the underlying pathological malfunctions. The effect of astrocytes on the activity of neuron-astrocyte networks has been analysed with computational models. These can reproduce experimentally observed phenomena, such as astrocytic modulation of spike and burst signalling in neuron-astrocyte networks. Using an established computational neuron-astrocyte network model, we simulate experimental data of healthy and pathological networks by using different neuronal and astrocytic parameter configurations. In our simulations, the reduction of neuronal or astrocytic cell densities yields decreased glutamate levels and a statistically significant reduction in the network activity. Amplifications of the astrocytic ATP release toward postsynaptic terminals also reduced the network activity and resulted in temporarily increased glutamate levels. In contrast, reducing either the glutamate release or re-uptake in astrocytes resulted in higher network activities. Similarly, an increase in synaptic weights of excitatory or inhibitory neurons raises the excitability of individual cells and elevates the activation level of the network. To conclude, our simulations suggest that the impairment of both neurons and astrocytes disturbs the neuronal network activity in schizophrenia.

中文翻译：

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精神分裂症的神经元和星形胶质细胞调节：计算模型研究。

根据三方突触模型，星形胶质细胞对神经元信号传递具有调节作用。最近，星形胶质细胞功能障碍与精神分裂症等精神疾病有关。关于精神分裂症中星形胶质细胞的病理机制，已经提出了几种假设。例如，尸检显示精神分裂症患者的星形胶质细胞密度降低。另一种假说表明，疾病症状与谷氨酸传输异常有关，谷氨酸传输异常也受到星形胶质细胞的调节（精神分裂症的谷氨酸假说）。电生理学研究结果表明，对于这种疾病是否会导致神经元和星形细胞活动增加或减少存在争议。此外，对于精神分裂症中哪些分子途径和网络机制发生改变还没有达成共识。计算模型可以帮助发现潜在的病理故障。已经用计算模型分析了星形胶质细胞对神经元-星形胶质细胞网络活动的影响。这些可以重现实验观察到的现象，例如神经元星形胶质细胞网络中尖峰和爆发信号的星形胶质细胞调节。使用已建立的计算神经元-星形胶质细胞网络模型，我们通过使用不同的神经元和星形胶质细胞参数配置来模拟健康和病理网络的实验数据。在我们的模拟中，神经元或星形细胞密度的减少会导致谷氨酸水平降低，并且网络活动在统计上显着减少。星形胶质细胞 ATP 向突触后末端释放的放大也减少了网络活动并导致谷氨酸水平暂时升高。相反，减少星形胶质细胞中谷氨酸的释放或重新摄取会导致更高的网络活动。同样，兴奋性或抑制性神经元突触权重的增加会提高单个细胞的兴奋性并提高网络的激活水平。总之，我们的模拟表明神经元和星形胶质细胞的损伤会扰乱精神分裂症的神经元网络活动。