Increasing pieces of evidence have suggested that astrocyte function has a strong influence on neuronal activity and plasticity, both in physiological and pathophysiological situations. In epilepsy, astrocytes have been shown to respond to epileptic neuronal seizures; however, whether they can act as a trigger for seizures has not been determined. Here, using the copper implantation method, spontaneous neuronal hyperactivity episodes were reliably induced during the week following implantation. With near 24‐h continuous recording for over 1 week of the local field potential with in vivo electrophysiology and astrocyte cytosolic Ca2+ with the fiber photometry method, spontaneous occurrences of seizure episodes were captured. Approximately 1 day after the implantation, isolated aberrant astrocyte Ca2+ events were often observed before they were accompanied by neuronal hyperactivity, suggesting the role of astrocytes in epileptogenesis. Within a single developed episode, astrocyte Ca2+ increase preceded the neuronal hyperactivity by ~20 s, suggesting that actions originating from astrocytes could be the trigger for the occurrence of epileptic seizures. Astrocyte‐specific stimulation by channelrhodopsin‐2 or deep‐brain direct current stimulation was capable of inducing neuronal hyperactivity. Injection of an astrocyte‐specific metabolic inhibitor, fluorocitrate, was able to significantly reduce the magnitude of spontaneously occurring neuronal hyperactivity. These results suggest that astrocytes have a role in triggering individual seizures and the reciprocal astrocyte‐neuron interactions likely amplify and exacerbate seizures. Therefore, future epilepsy treatment could be targeted at astrocytes to achieve epilepsy control.

中文翻译：

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星形胶质细胞切换到过度活跃模式

越来越多的证据表明，星形胶质细胞的功能对生理和病理生理情况下的神经元活动和可塑性都有很大影响。在癫痫症中，星形胶质细胞已被证明对癫痫神经元发作有反应。然而，它们是否可以触发癫痫发作尚未确定。在这里，使用铜植入方法，在植入后一周内可靠地诱导了自发性神经元过度活跃发作。通过体内电生理学和星形胶质细胞胞质 Ca2+ 近 24 小时连续记录超过 1 周的局部场电位2+通过光纤光度测定法，可以捕捉到癫痫发作的自发发生。植入后约 1 天，分离出异常星形胶质细胞 Ca2+事件经常在伴随神经元过度活跃之前被观察到，这表明星形胶质细胞在癫痫发生中的作用。在单个发育事件中，星形胶质细胞 Ca2+增加先于神经元过度活跃约 20 秒，表明星形胶质细胞的活动可能是癫痫发作发生的触发因素。通道视紫红质-2 或深部脑直流电刺激的星形胶质细胞特异性刺激能够诱导神经元过度活跃。注射星形胶质细胞特异性代谢抑制剂氟柠檬酸盐能够显着降低自发发生的神经元过度活跃的程度。这些结果表明星形胶质细胞在触发个体癫痫发作中发挥作用，并且星形胶质细胞与神经元的相互作用可能会放大和加剧癫痫发作。因此，未来的癫痫治疗可以针对星形胶质细胞来实现癫痫控制。