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

点击翻译按钮获取中文摘要

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.