The signalling pathways involved in NMDA receptor-dependent LTD

NMDA 受体依赖性 LTD 涉及的信号通路

• 批准号: BB/H006451/1
• 负责人: Graham Collingridge
• 金额: $ 51.92万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH006451%2F1
• 关键词: signalling; pathways; involved; NMDA; receptor

Information storage in the brain depends on changes in the efficiency by which nerve cells (neurons) communicate. This occurs at specialised structures (synapses) via the release of a chemical neurotransmitter and its detection by receptor proteins, a process called synaptic transmission. The strength of this communication can be increased or decreased, depending on the patterns of synaptic activation, i.e. synaptic plasticity. In general, synaptic transmission can be increased by the process known as long-term potentiation (LTP) or decreased by the process known as long-term depression (LTD). The best established forms of synaptic plasticity involve the activation of one class of L-glutamate receptor, the NMDA receptor, which leads to alterations in the number of another class of glutamate receptor, the AMPA receptor, at synapses. The aim of the proposed project is to find the mechanisms by which NMDA receptor activation leads to a decrease in AMPA receptor transmission during LTD in the hippocampus, a brain region critically involved in learning and memory. We have recently discovered two proteins that appear to play a central role in this process. The purpose of this project is to identify how these proteins are involved in this important form of synaptic plasticity.

大脑中的信息存储取决于神经细胞（神经元）传达的效率的变化。这是通过化学神经递质释放及其通过受体蛋白检测的专业结构（突触）发生的，该过程称为突触传播。根据突触激活的模式，即突触可塑性，这种通信的强度可以增加或降低。通常，突触传播可以通过称为长期增强（LTP）的过程增加，也可以通过称为长期抑郁症（LTD）的过程减少。最佳建立的突触可塑性形式涉及一类L-谷氨酸受体NMDA受体的激活，这会导致突触中另一种类别的谷氨酸受体AMPA受体的数量改变。拟议项目的目的是找到NMDA受体激活导致Hippocampus期间AMPA受体传播减少的机制，Hippocampus是一个严重涉及学习和记忆的大脑区域。最近，我们发现了两种在此过程中似乎起着核心作用的蛋白质。该项目的目的是确定这些蛋白质如何参与这种重要形式的突触可塑性。