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

脑功能是由两类细胞介导的，即可电兴奋的神经元和不可电兴奋的神经胶质细胞。一个多世纪以来，神经胶质细胞被认为扮演着结构和营养支持神经元的角色。甚至他们的名字的意思是“胶水”（在希腊语中）。神经胶质细胞的数量是神经元的10:1，这就产生了一个流行的陈词滥调：“我们只利用了大脑10%的潜力”。近年来，人们对胶质细胞/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讯的有力参与者，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。神经胶质细胞也成为开发治疗神经退行性疾病药物的新靶点。我的项目将研究皮层星形胶质细胞中由谷氨酸产生的信号，谷氨酸是一种非常重要的神经元通讯递质。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谷氨酸等“经典”神经递质介导的信号的能力。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。这些对许多脑功能至关重要，如记忆和认知，以及许多脑病理，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小组提供了新的见解。他们已经证明，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受体也可能是开发新的神经系统疾病治疗剂的有希望的靶点。然而，目前关于星形胶质细胞NMDA受体的特性和功能的不完整的知识阻碍了这一点。我的项目将首次详细研究皮层星形胶质细胞中NMDA受体的特性及其在星形胶质细胞信号传导中的作用。我的研究成果将对神经胶质NMDA受体的药理和功能特性有新的认识。

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.