Synaptic Metaplasticity through NMDA Receptor Lateral Diffusion
Synaptic Metaplasticity through NMDA Receptor Lateral Diffusion
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DOI：
10.1523/jneurosci.5450-07.2008
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发表时间：
2008-03
期刊：
影响因子：
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通讯作者：
Jiang-Ping Zhao;Yi Peng;Zhuo Xu;Rong-qing Chen;Q. Gu;Zheng Chen;W. Lu
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文献类型：
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作者：
Jiang-Ping Zhao;Yi Peng;Zhuo Xu;Rong-qing Chen;Q. Gu;Zheng Chen;W. Lu
谷氨酸受体的横向扩散被认为是调节突触受体数量并影响突触功能，特别是突触传递效率的机制。然而，受体横向扩散与突触功能变化之间的直接联系尚未确定。在本研究中，我们通过检测 (+)-MK-801 [(+)-5-甲基-10,11-二氢-5H-二苯并 [a,d] 环庚烯-5,10-亚胺块中自发或诱发 EPSC 的大量恢复，证明了海马切片 CA1 神经元中 NMDA 受体 (NMDAR) 的横向扩散。 maleate]，一种不可逆的 NMDAR 开放通道阻断剂。我们观察到恢复后突触 NMDAR 的数量和组成发生变化。更重要的是，恢复后，产生长时程增强（LTP）的方案仅诱导LTD（长期抑制）而不是LTP。相比之下，观察到竞争性 NMDAR 阻滞剂 d,l-AP-5 完全恢复，而突触可塑性没有随后的变化。我们的数据表明 NMDAR 运输的修正模型，其中突触外 NMDAR（主要是 NR1/NR2B 受体）横向移动到突触位点，导致突触修饰规则发生改变。因此，CA1突触表现出一种新的化塑性形式，其中突触修饰的方向可以通过NMDA受体的亚型特异性横向扩散来逆转。
Lateral diffusion of glutamate receptors was proposed as a mechanism for regulating receptor numbers at synapses and affecting synaptic functions, especially the efficiency of synaptic transmission. However, a direct link between receptor lateral diffusion and change in synaptic function has not yet been established. In the present study, we demonstrated NMDA receptor (NMDAR) lateral diffusion in CA1 neurons in hippocampal slices by detecting considerable recovery of spontaneous or evoked EPSCs from the block of (+)-MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an irreversible NMDAR open-channel blocker. We observed changes on both the number and the composition of synaptic NMDAR on recovery. More importantly, after the recovery, long-term potentiation (LTP)-producing protocol induced only LTD (long-term depression) instead of LTP. In contrast, a complete recovery from competitive NMDAR blocker d,l-AP-5 was observed without subsequent changes on synaptic plasticity. Our data suggest a revised model of NMDAR trafficking wherein extrasynaptic NMDARs, mostly NR1/NR2B receptors, move laterally into synaptic sites, resulting in altered rule of synaptic modification. Thus, CA1 synapses exhibit a novel form of metaplasticity in which the direction of synaptic modification can be reverted through subtype-specific lateral diffusion of NMDA receptors.