Dynamics Of Excitatory Synaptic Transmission In The Cns

大脑在庞大的神经元网络中以突触连接的方式存储信息。新的信息通过不完全了解的机制通过连接的修改被纳入神经网络。一个基本问题是，单个连接是独立运作，还是受到邻近突触活动的影响。突触连接是通过释放可扩散的神经递质分子来实现的，这些递质分子与受体神经元上的受体结合；最近的证据表明，神经递质可能会逃离释放它的突触，扩散到邻近的突触。神经递质在突触连接之间的这种“溢出”将对神经网络的信息容量及其在发育过程中构建的机制产生深远的影响。该实验室的工作旨在确定兴奋性神经递质谷氨酸是否会在海马体（大脑中学习和记忆存储的主要部位）和视网膜（视觉刺激被编码并沿视神经传递的地方）的突触之间溢出。我们利用电生理技术在大鼠视网膜和海马的急性制备切片中发现，谷氨酸从其释放的突触中逃脱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控，谷氨酸转运蛋白主要位于结合谷氨酸并将其从脑脊液中移除的胶质膜上。此外，受体神经元的电状态似乎影响受体是否对远端突触释放的低水平谷氨酸作出反应。研究这些机制的调节及其对神经元网络信息处理的影响的工作仍在继续。

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.