NMDA AND NON-NMDA RECEPTORS ARE CO-LOCALIZED AT INDIVIDUAL EXCITATORY SYNAPSES IN CULTURED RAT HIPPOCAMPUS

NMDA AND NON-NMDA RECEPTORS ARE CO-LOCALIZED AT INDIVIDUAL EXCITATORY SYNAPSES IN CULTURED RAT HIPPOCAMPUS
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DOI:
10.1038/341230a0
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发表时间:
1989-09-21
期刊:
影响因子:
64.8
通讯作者:
STEVENS, CF
STEVENS, CF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BEKKERS, JM;STEVENS, CF

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关于海马长时程增强的一个中心假设是,两类谷氨酸受体离子通道,N-甲基-D-天冬氨酸(NMDA)和红藻氨酸/使君子氨酸(非NMDA)亚型,共同定位于单个兴奋性突触1,2。这一假设很重要,因为在长时程增强的诱导和表达中,NMDA和非NMDA受体之间存在相互作用:NMDA类凭借其被镁3,4和钙渗透性5,6阻断的电压依赖性通道,为诱导长时程增强提供了触发,而突触功效的实际增强被认为是由非提供的。-如果两种受体亚型都存在于一个突触上,这种交叉调制可能会通过扩散因子快速局部发生。通过测量培养的海马神经元的微型突触电流,我们发现,大多数(约70%)的兴奋性突触的突触后细胞具有这两种受体,虽然在不同程度上。在其余的兴奋性突触中,约20%只含有非NMDA受体亚型,其余仅含有NMDA受体。这一发现为谷氨酸受体亚型在单个突触上的共定位提供了直接证据,也指出了长时程增强可能根据该突触上受体亚型的混合而在每个突触上差异表达的可能性。
A CENTRAL assumption about long-term potentiation in the hip-pocampus is that the two classes of glutamate-receptor ion channel, theN-methyl-D-aspartate (NMDA) and the kainate/quisqualate (non-NMDA) subtypes, are co-localized at individual excitatory synapses1,2. This assumption is important because of the perceived interplay between NMDA and non-NMDA receptors in the induc-tion and expression of long-term potentiation: the NMDA class, by virtue of its voltage-dependent channel block by magnesium3,4and calcium permeability5,6, provides the trigger for the induction of long-term potentiation, whereas the actual enhancement of synaptic efficacy is thought to be provided by the non-NMDA class7,9. If both receptor subtypes are present at the one synapse, such cross-modulation could occur rapidly and locally through diffusible factors. By measuring miniature synaptic currents in cultured hippocampal neurons we show that the majority (∼70%) of the excitatory synapses on a postsynaptic cell possess both kinds of receptor, although to different extents. Of the remaining excita-tory synapses, ∼20% contain only the non-NMDA subtype and the rest possess only NMDA receptors. This finding provides direct evidence for co-localization of glutamate-receptor subtypes at individual synapses, and also points to the possibility that long-term potentiation might be differentially expressed at each synapse according to the mix of receptor subtypes at that synapse.