Dynamics Of Excitatory Synaptic Transmission In The Cns

中枢神经系统兴奋性突触传递的动力学

• 批准号: 6501282
• 负责人: JEFFREY S DIAMOND
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6501282
• 关键词: NMDA receptors; amacrine cells; central nervous system; cerebrospinal fluid; developmental neurobiology; electrophysiology; glia; glutamate transporter; glutamates; hippocampus; laboratory rat; neural information processing; neural transmission; neurotransmitter receptor; pyramidal cells; receptor binding; retina; retinal ganglion; synapses; visual stimulus

The brain stores information in patterns of synaptic connections within large networks of neurons. New information is incorporated into a neural network through the modification of connections via mechanisms that are incompletely understood. One fundamental question is whether individual connections behave independently, or whether they are influenced by the activity of neighboring synapses. Synaptic connections are made through the release of diffusible neurotransmitter molecules that bind to receptors on the recipient neuron; recent evidence suggests that the neurotransmitter may escape the synapse in which it is released and diffuse into neighboring synapses. This "spillover" of neurotransmitter between synaptic connections would have a profound impact on the information capacity of neural networks and the mechanisms by which they are constructed during development. Work in this laboratory is directed towards determining whether the excitatory neurotransmitter glutamate spills over between synapses in the hippocampus, a major site of learning and memory storage in the brain, and in the retina, where visual stimuli is encoded for transmission along the optic nerve. Using electrophysiological techniques in acutely prepared slices of rat retina and hippocampus, we have found that glutamate escapes the synapse from which it is released and diffuses into neighboring synapses. This diffusion is tightly regulated by glutamate transporters, pump proteins located primarily on glial membranes that bind glutamate and remove it from the cerebrospinal fluid. Moreover, it appears that the electrical state of the recipient neuron influence whether the receptors are responsive to low levels of glutamate released from a distant synapse. Work is continuing to investigate the modulation of these mechanisms and their impact on information processing in networks of neurons.

大脑以突触连接的模式将信息存储在大型神经元网络中。新的信息通过不完全理解的机制修改连接而被纳入神经网络。一个基本的问题是，各个连接是否独立地起作用，或者它们是否受到相邻突触活动的影响。突触连接是通过释放与受体神经元上的受体结合的可扩散神经递质分子来实现的;最近的证据表明，神经递质可能会逃离释放它的突触并扩散到相邻的突触中。突触连接之间的神经递质的这种“溢出”将对神经网络的信息容量以及它们在发育过程中构建的机制产生深远的影响。这个实验室的工作是确定兴奋性神经递质谷氨酸是否溢出海马体和视网膜中的突触之间，海马体是大脑中学习和记忆存储的主要场所，而视网膜中的视觉刺激是编码的，以便沿着视神经传输。利用电生理技术在急性制备的大鼠视网膜和海马切片中，我们发现谷氨酸从释放它的突触逃逸并扩散到邻近的突触中。这种扩散受到谷氨酸转运蛋白的严格调节，谷氨酸转运蛋白主要位于神经胶质细胞膜上，结合谷氨酸并将其从脑脊液中清除。此外，似乎受体神经元的电状态影响受体是否对从远端突触释放的低水平谷氨酸有反应。目前正在继续研究这些机制的调制及其对神经元网络信息处理的影响。