Brain glycogen is mainly stored in astrocytes. However, recent studies both in vitro and in vivo indicate that glycogen also plays important roles in neurons. By conditional deletion of glycogen synthase (GYS1), we previously developed a mouse model entirely devoid of glycogen in the central nervous system (GYS1^Nestin-KO). These mice displayed altered electrophysiological properties in the hippocampus and increased susceptibility to kainate-induced seizures. To understand which of these functions are related to astrocytic glycogen, in the present study, we generated a mouse model in which glycogen synthesis is eliminated specifically in astrocytes (GYS1^Gfap-KO). Electrophysiological recordings of awake behaving mice revealed alterations in input/output curves and impaired long-term potentiation, similar, but to a lesser extent, to those obtained with GYS1^Nestin-KO mice. Surprisingly, GYS1^Gfap-KO mice displayed no change in susceptibility to kainate-induced seizures as determined by fEPSP recordings and video monitoring. These results confirm the importance of astrocytic glycogen in synaptic plasticity.

脑糖原主要储存在星形胶质细胞中。然而，最近的体外和体内研究表明，糖原在神经元中也起着重要作用。通过有条件地删除糖原合酶 (GYS1)，我们之前开发了一种中枢神经系统中完全没有糖原的小鼠模型 (GYS1 ^Nestin-KO )。这些小鼠在海马体中表现出改变的电生理特性，并且对红藻氨酸诱导的癫痫发作的易感性增加。为了了解这些功能中的哪些与星形胶质细胞糖原有关，在本研究中，我们生成了一个小鼠模型，其中糖原合成在星形胶质细胞中被特异性消除（GYS1 ^Gfap-KO）。清醒行为小鼠的电生理记录显示输入/输出曲线的改变和长期增强功能受损，与 GYS1 ^Nestin-KO小鼠相似，但程度较轻。令人惊讶的是，通过 fEPSP 记录和视频监测确定，GYS1 ^Gfap-KO小鼠对红藻氨酸诱导的癫痫发作的易感性没有变化。这些结果证实了星形细胞糖原在突触可塑性中的重要性。