Properties and function of astroglial NMDA receptors: implications for plasticity of neuron-glial communication in the neocortex

脑功能由两类细胞介导，即电可兴奋神经元和电不可兴奋神经胶质细胞。世纪以来，胶质细胞被认为是结构和营养支持神经元的作用。甚至他们的名字的意思是“胶水”（希腊语）。神经胶质细胞的数量超过神经元10：1，这就产生了一个流行的陈词滥调，即“我们只利用了大脑10%的潜力”。近年来，对胶质细胞/星形胶质细胞和少突胶质细胞功能的认识发生了革命性的变化。今天，神经胶质细胞被认为是大脑通信的有效参与者，神经科学实验室对星形胶质细胞和少突胶质细胞研究的兴趣正在迅速增长。神经胶质细胞也已成为开发用于治疗神经变性病症的治疗剂的新靶标。我的项目将研究谷氨酸在皮质星形胶质细胞中产生的信号-谷氨酸是神经元通信的一种非常重要的传递物质。在过去十年中获得的数据已经证明了神经胶质细胞产生和接收由“经典”神经递质如谷氨酸介导的信号的能力。谷氨酸作为递质的作用是由几种类型的受体介导的。其中最重要的是NMDA受体。这些对于许多大脑功能至关重要，如记忆和认知以及许多大脑病理学，如缺血和各种神经退行性疾病。直到最近，NMDA受体被认为对神经胶质细胞的功能不是很重要。在这一领域开展工作的少数几个团体提供了新的见解。他们已经表明，神经胶质NMDA受体具有不同于神经元的特性，并有助于神经元和神经胶质细胞之间的信号传导。神经胶质NMDA受体也可能是开发神经系统疾病新型治疗药物的有前途的靶点。然而，这是阻碍了目前的知识不完整的性质和功能的星形胶质细胞NMDA受体。我的项目将提供第一个详细的调查性质的NMDA受体在皮层星形胶质细胞和他们的作用，星形胶质细胞的信号。本论文的研究成果将为神经胶质NMDA受体的药理学和功能特性提供新的认识。

Brain function is mediated by two classes of cell, the electrically excitable neurons and electrically non-excitable glial cells. For more than a century, glial cells were thought to play the role of structural and nutritional support neurons. Even their name means 'glue' (in Greek). Glial cells outnumber neurons 10:1 and this gives rise to the popular cliché that 'we use the potential of our brain only for 10 %'. The view on the function of glial cells / astrocytes and oligodendrocytes has undergone revolutionary change in recent years. Today glial cells are recognized as competent participants of brain communications and the interest of neuroscience laboratories in astrocyte and oligodendrocyte studies is rapidly growing. Glial cells have also become new targets for developing therapeutic agents for treatment of neurodegenerative disorders. My project will study signals generated in cortical astrocytes by glutamate - a very important transmitter of neuronal communications. Data obtained in the last decade have demonstrated the capability of glial cells to generate and receive signals mediated by 'classical' neurotransmitters such as glutamate. The actions of glutamate as a transmitter are mediated by several types of receptors. Of these, one of the most important is the NMDA receptor. These are critical for many brain functions, like memory and cognition and many brain pathologies such as ischemia and various neurodegenerative disorders. Until recently, NMDA receptors were thought not to be very important for the function of glial cells. The few groups who have undertaken work in this area have provided new insights. They have shown that glial NMDA receptors have properties different from neuronal ones and contribute to signaling between neurons and glial cells. Glial NMDA receptors may also be promising targets for the development of novel therapeutic agents for neurological disorders. However, this is hampered by incomplete current knowledge about the properties and functions of astroglial NMDA receptors. My project will provide the first detailed investigation of properties of NMDA receptors in the cortical astrocytes and their role in the astrocyte signalling. The outcome of my research will be new understanding of the pharmacological and functional properties of glial NMDA receptors.