Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002-Madrid, Spain.
J Neurosci. 2010 Aug 18;30(33):11032-42. doi: 10.1523/JNEUROSCI.1848-10.2010.
We had described a muscarinic-mediated long-term synaptic enhancement at Schaffer collateral synapses caused by the insertion of AMPARs in spines of rat hippocampal CA1 pyramidal neurons that requires Ca(2+) release from IP3-sensitive stores (Fernández de Sevilla et al., 2008). We now show that this AMPA-mediated LTP(IP3) is precisely matched by an amplification of NMDAR-mediated transmission. The enhanced AMPAR transmission involves SNARE protein activity and CaMKII activation. The amplification of NMDA transmission requires combined CaMKII, PKC, and SRC kinase activity without detectable surface incorporation of NMDARs, suggesting that changes in receptor properties mediate this process. The enhanced AMPAR- and NMDAR-mediated transmission markedly reduce the induction threshold of "Hebbian" LTP. We conclude that both modes of glutamatergic synaptic potentiation may play a critical functional role in the regulation of the learning machinery of the brain by adding flexibility to the demands of the hippocampal network.
我们曾描述过一种在大鼠海马 CA1 锥体神经元的棘突中 AMPAR 插入所引起的、由毒蕈碱能介导的长时程突触增强，该增强需要 IP3 敏感库中的 Ca2+释放（Fernández de Sevilla 等人，2008）。我们现在表明，这种 AMPA 介导的 LTP（IP3）与 NMDA 受体介导的传递的放大精确匹配。增强的 AMPAR 传递涉及 SNARE 蛋白活性和 CaMKII 激活。NMDA 传递的放大需要 CaMKII、PKC 和 SRC 激酶的联合活性，而 NMDA 受体的表面掺入则没有可检测到，这表明受体特性的变化介导了这个过程。增强的 AMPAR 和 NMDA 受体介导的传递显著降低了“Hebbian”LTP 的诱导阈值。我们的结论是，这两种谷氨酸能突触增强模式可能通过为海马网络的需求增加灵活性，在大脑学习机制的调节中发挥关键的功能作用。
