Lack of NMDA receptor subtype selectivity for hippocampal long-term potentiation
Lack of NMDA receptor subtype selectivity for hippocampal long-term potentiation
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DOI：
10.1523/jneurosci.1905-05.2005
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发表时间：
2005-07-20
影响因子：
5.3
通讯作者：
Köhr, G
中科院分区：
文献类型：
--
作者：
Berberich, S;Punnakkal, P;Köhr, G
NMDA 受体 (NMDAR) 2A (NR2A) 型和 NR2B 型 NMDAR 共存于 CA1 锥体细胞的突触中。最近使用 NMDAR 亚型药物阻断的研究提出，NR2A 型负责诱导长时程增强 (LTP)，而 NR2B 型则诱导长时程抑制 (LTD)。这与在转基因小鼠中的发现形成鲜明对比，即当 NR2A 信号传导缺失或受损时，NR2B 型 NMDAR 会诱导 LTP，尽管补偿机制可能促成了这一结果。因此，我们通过不同的诱导方案并在 NMDAR 拮抗剂（包括 NR2A 型阻断剂 NVP-AAM077）存在下评估了两种 NMDAR 亚型对小鼠海马切片中 LTP 的贡献，其中确定了重组和天然 NMDAR 亚型选择性的最佳浓度。通过优先拮抗 NR2A 型或 NR2B 型 NMDAR 或通过非选择性拮抗剂 D-AP-5 将 NMDA EPSC 部分阻断 40%，不会损害 LTP，这表明海马 LTP 诱导可由任一 NMDAR 亚型产生。
NMDA receptor (NMDAR) 2A (NR2A)- and NR2B-type NMDARs coexist in synapses of CA1 pyramidal cells. Recent studies using pharmacological blockade of NMDAR subtypes proposed that the NR2A type is responsible for inducing long-term potentiation (LTP), whereas the NR2B type induces long-term depression (LTD). This contrasts with the finding in genetically modified mice that NR2B-type NMDARs induce LTP when NR2A signaling is absent or impaired, although compensatory mechanisms might have contributed to this result. We therefore assessed the contribution of the two NMDAR subtypes to LTP in mouse hippocampal slices by different induction protocols and in the presence of NMDAR antagonists, including the NR2A-type blocker NVP-AAM077, for which an optimal concentration for subtype selectivity was determined on recombinant and native NMDARs. Partial blockade of NMDA EPSCs by 40%, either by preferentially antagonizing NR2A- or NR2B-type NMDARs or by the nonselective antagonist D-AP-5, did not impair LTP, demonstrating that hippocampal LTP induction can be generated by either NMDAR subtype.