Modulation of AMPA receptor unitary conductance by synaptic activity

Modulation of AMPA receptor unitary conductance by synaptic activity
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DOI:
10.1038/31709
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发表时间:
1998-06-25
期刊:
影响因子:
64.8
通讯作者:
Collingridge, GL
Collingridge, GL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Benke, TA;Lüthi, A;Collingridge, GL

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突触强度的活动依赖性改变是脊椎动物中枢神经系统的基本特性,被认为是学习和记忆的基础。活动依赖性突触可塑性研究最广泛的模型是谷氨酸响应(谷氨酸)突触的长时程增强 (LTP),这是一种涉及多种机制的广泛现象(1)。 LTP 的最佳表征形式发生在海马 CA1 区,其中 LTP 由 NMDA(N-甲基-D-天冬氨酸)受体瞬时激活启动,并表现为通过 AMPA(α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯)受体突触传递持续增加 (2)。这种增加至少部分是由于 AMPA 受体功能的突触后修饰(3);这种修饰可能是由受体数量、开放概率、动力学或单通道电导的增加引起的。在这里,我们发现海马 CA1 区 LTP 的诱导通常与 AMPA 受体单通道电导的增加有关。这表明基本通道特性可以通过突触活动快速改变,并提供了对谷氨酸突触改变其强度的一种分子机制的深入了解。
Activity-dependent alteration in synaptic strength is a fundamental property of the vertebrate central nervous system and is thought to underlie learning and memory. The most extensively studied model of activity-dependent synaptic plasticity is longterm potentiation (LTP) of glutamate-responsive (glutamatergic) synapses, a widespread phenomenon involving multiple mechanisms(1). The best characterized form of LTP occurs in the CA1 region of the hippocampus, in which LTP is initiated by transient activation of NMDA (N-methyl-D-aspartate) receptors and is expressed as a persistent increase in synaptic transmission through AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole pionate) receptors(2). This increase is due, at least in part, to a postsynaptic modification of AMPA-receptor function(3); this modification could be caused by an increase in the number of receptors, their open probability, their kinetics or their single-channel conductance. Here we show that the induction of LTP in the CA1 region of the hippocampus is often associated with an increase in single-channel conductance of AMPA receptors. This shows that elementary channel properties can be rapidly modified by synaptic activity and provides an insight into one molecular mechanism by which glutamatergic synapses can alter their strength.