Discovering novel subtype-selective glutamate receptor antagonists for the study of hippocampal synaptic plasticity

这项工作的主要目的是设计和合成新的化学物质，用作研究学习和记忆基本机制的工具。这项研究可能会为涉及认知功能障碍的疾病带来新的治疗方法，如精神分裂症，阿尔茨海默氏症和帕金森氏症。大脑中一个神经细胞（神经元）和其他神经细胞之间的通讯是在连接处（突触）进行的。神经元链中的一个细胞与下一个细胞沟通的主要机制之一是从其多个突触末端释放氨基酸谷氨酸。我们已经帮助建立了谷氨酸可以与一系列结构相关的蛋白质相互作用，这些蛋白质被称为谷氨酸受体亚型，每个亚型在中枢神经系统（CNS）中执行不同的功能。鉴于谷氨酸激活谷氨酸受体的所有亚型，我们的目标是生产只阻断一种受体亚型激活的工具。通过观察特定谷氨酸受体亚型的特异性激活或阻断对中枢神经系统功能的影响，人们可以推断出该受体亚型在构成学习和记忆基础的神经活动综合模式中的特定作用。

The main aim of this work is to design and synthesize new chemical substances to be used as tools to investigate the fundamental mechanism of learning and memory. This research may lead to new treatments for disorders that involve cognitive dysfunction, such as schizophrenia, Alzheimer’s and Parkinson’s disease. Communication between one nerve cell (neuron) and others in the brain is effected at the junctions (synapses). One of the main mechanisms by which one cell in a neuronal chain communicates with the next cell is by releasing an amino acid, glutamate from its multiple synaptic endings. We have helped establish that glutamate can interact with a family of structurally related proteins known as glutamate receptor subtypes each performing different functions in the central nervous system (CNS). Whereas glutamate activates all the subtypes of glutamate receptor, we aim to produce tools that block the activation of only one subtype of receptor. By observing what effect specific activation or blockade of a particular glutamate receptor subtype has on the functioning of the CNS, one can deduce the particular role of that receptor subtype in the integrated pattern of nervous activity that underlies learning and memory.