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Functional modeling of astrocytes in epilepsy: a feedback system perspective

机译：癫痫中星形胶质细胞的功能建模：反馈系统的角度

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摘要

Astrocytes, a subtype of glial cells, in the brain provide structural and metabolic supports to the nervous system. They are also active partners in synaptic transmission and neuronal activities. In the present study, a biologically plausible thalamocortical neural population model (TCM) originally proposed by Suffczynski et al. (Neuroscience 126(2):467-484, 2004) is extended by integrating the functional role of astrocytes in the regulation of synaptic transmission. Therefore, the original TCM is modified to consider neuron-astrocyte interactions. Using the modified model, it is demonstrated that the healthy astrocytes are capable to compensate the variation of cortical excitatory input by increasing their firing frequency. In this way, they can preserve the attractor corresponding to the normal activity. Furthermore, the performance of the pathological astrocytes is also investigated. It is hypothesized that one of the plausible causes of seizures is the malfunction of astrocytes in the regulatory feedback loop. That is, pathologic astrocytes are not any more able to regulate and/or compensate the excessive increase of the cortical input. Therefore, pathologic astrocytes lead to the emergence of paroxysmal attractor. Results demonstrate that disruption of the homeostatic or signaling function of astrocytes can initiate the synchronous firing of neurons, suggesting that astrocytes might be one of the potential targets for the treatment of epilepsy.
机译：星形细胞是神经胶质细胞的一种亚型，在大脑中为神经系统提供结构和代谢支持。他们还是突触传递和神经元活动的积极伙伴。在本研究中，最初由Suffczynski等人提出的生物学上合理的丘脑皮质神经种群模型（TCM）。 （Neuroscience 126（2）：467-484，2004）通过整合星形胶质细胞在调节突触传递中的功能作用而得到扩展。因此，对原始中医进行了修改以考虑神经元-星形胶质细胞的相互作用。使用修改后的模型，可以证明健康的星形胶质细胞能够通过增加其激发频率来补偿皮质兴奋性输入的变化。这样，它们可以保存与正常活动相对应的吸引子。此外，还研究了病理性星形胶质细胞的性能。据推测，癫痫发作的可能原因之一是调节反馈回路中的星形胶质细胞功能异常。也就是说，病理性星形胶质细胞不再能够调节和/或补偿皮质输入的过度增加。因此，病理性星形胶质细胞导致发作性吸引子的出现。结果表明，星形胶质细胞稳态或信号功能的破坏可以引发神经元的同步放电，这表明星形胶质细胞可能是治疗癫痫的潜在靶标之一。

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