已知兴奋性氨基酸转运体EAAT调节神经突触活动，维持神经系统微环境稳定，在脑缺血损伤和退行性神经疾病有重要作用。目前EAAT表达的调控机制研究甚为缺乏。Rheb/mTOR信号是调节蛋白质合成和细胞生长的主要途径之一，但未知其对于EAAT表达的调节作用。我们的前期研究首次发现：在星形胶质细胞中加入mTOR的抑制剂rapamycin可以增加谷氨酸转运体GLT1的表达。本课题将利用原代神经元和胶质细胞培养、分子生物学、细胞生物学、全细胞膜片钳电生理记录，并结合Rheb1基因敲除小鼠等手段，研究：1.星形胶质细胞和神经元中mTOR到Akt的反馈通路；2.mTORC1和mTORC2信号通过此反馈通路调节GLT1表达的机制及其在OGD模型中的作用；3.此信号通路在突触传递和脑缺血缺氧造成的神经元损伤中的作用。本研究结果将推进理解GLT1的调节机制，对研究神经系统疾病和学习记忆的机理起指导作用。

It is known that excitatory amino acid transporters (EAATs) play important roles in modulating synaptic activity and maintaining the equlibrium of neuronal micro-environment, and participate in the brain ischemia and neurodegenerative diseases. However, the modulatory mechanisms of EAATs are poorly understood. Rheb/mTOR pathway is a critical signaling to regulate the protein synthesis and cell growth, but it is unkown whether Rheb/mTOR modulates the expression of EAATs. Our preliminary results indicate that the inhibitor of mTOR, rapamycine, induces the increase of GLT1 expression in cultured astrocytes. In this study, we will combine various techniques, including primary cell culture, molecular biology, cellular biology, whole-cell patach-clamp recording and conditional Rheb1 knock-out mice, to investigate: 1) the feedback pathway from mTOR to Akt in neurons and astrocytes; 2) the mechanisms of mTORC1 and mTORC2 of GLT1 expression and its roles in OGD; 3) the roles of mTOR-Akt feedback signaling in synaptic transmission and MCAO model. Our results will push forward the current understandings of the modulatory mechanisms of GLT1 expression and give hints on the studies of mechanisms of neurological diseases and learning and memory.