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The Journal of Neuroscience, July 8, 2009, 29(27):8764-8773; doi:10.1523/JNEUROSCI.1014-09.2009

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Development/Plasticity/Repair
Metaplastic Regulation of Long-Term Potentiation/Long-Term Depression Threshold by Activity-Dependent Changes of NR2A/NR2B Ratio

Zhuo Xu,^1,2 Rong-Qing Chen,^1,2 Qin-Hua Gu,^1,2 Jing-Zhi Yan,^1,2 Shan-Hui Wang,^1,2 Su-Yi Liu,^1,2 and Wei Lu^1,2,3,4

¹Department of Neurobiology, ²Key Laboratory for Neurodegenerative Disease of Jiangsu Province, ³Laboratory of Reproductive Medicine, and ⁴Key Laboratory for Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People's Republic of China

Correspondence should be addressed to Dr. Wei Lu, Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People's Republic of China. Email: lu{at}njmu.edu.cn

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.

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Received March 2, 2009; revised May 9, 2009; accepted June 2, 2009.

Correspondence should be addressed to Dr. Wei Lu, Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People's Republic of China. Email: lu{at}njmu.edu.cn

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