Xu Zhuo, Chen Rong-Qing, Gu Qin-Hua, Yan Jing-Zhi, Wang Shan-Hui, Liu Su-Yi, Lu Wei
Department of Neurobiology, Key Laboratory for Neurodegenerative Disease of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People's Republic of China.
J Neurosci. 2009 Jul 8;29(27):8764-73. doi: 10.1523/JNEUROSCI.1014-09.2009.
In vivo experience induces changes in synaptic NMDA receptor (NMDAR) subunit components, which are correlated with subsequent modifications of synaptic plasticity. However, little is known about how these subunit changes regulate the induction threshold of subsequent plasticity. At hippocampal Schaffer collateral-CA1 synapses, we first examined whether a recent history of neuronal activity could affect subsequent synaptic plasticity through its actions on NMDAR subunit components. We found that prior activity history produced by priming stimulations (PSs) across a wide range of frequencies (1-100 Hz) could induce bidirectional changes in the NR2A/NR2B ratio, which governs the threshold for subsequent long-term potentiation/long-term depression (LTP/LTD). Manipulating the NR2A/NR2B ratio through partial NR2 subunit blockade mimicked the PS regulation of the LTP/LTD threshold. Our results demonstrate that activity-dependent changes in the NR2A/NR2B ratio can be critical factors in metaplastic regulation of the LTP/LTD threshold.
体内经历会引起突触N-甲基-D-天冬氨酸受体（NMDAR）亚基组成的变化，这与随后突触可塑性的改变相关。然而，对于这些亚基变化如何调节随后可塑性的诱导阈值，人们了解甚少。在海马体的沙费尔侧支- CA1突触中，我们首先研究了近期的神经元活动历史是否会通过其对NMDAR亚基组成的作用来影响随后的突触可塑性。我们发现，通过在广泛频率范围（1 - 100赫兹）内进行引发刺激（PS）产生的先前活动历史，可诱导NR2A/NR2B比率发生双向变化，而该比率决定了随后长时程增强/长时程抑制（LTP/LTD）的阈值。通过部分NR2亚基阻断来操纵NR2A/NR2B比率，可模拟PS对LTP/LTD阈值的调节。我们的结果表明，NR2A/NR2B比率中依赖活动的变化可能是LTP/LTD阈值的元可塑性调节中的关键因素。
