NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII
NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII
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DOI：
10.1016/j.neuron.2005.08.034
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发表时间：
2005-10-20
期刊：
影响因子：
16.2
通讯作者：
Malinow, R
中科院分区：
文献类型：
--
作者：
Barria, A;Malinow, R
钙通过突触后NMDA-R进入和随后的CaMKII激活触发许多脑区的突触可塑性。活性CaMKII可以与NMDA-R结合，但这种相互作用的生理作用还没有很好地理解。在这里，我们测试，如果协会之间的活动CaMKII和突触NMDA-R是突触可塑性所需的。转换突触NR 2B的NMDA-R，结合CaMKII的高亲和力与那些含有NR 2A，一个亚基与CaMKII的低亲和力，显着降低LTP。具有增加与活性CaMKII的关联的突变的NR 2A的表达恢复LTP。最后，通过减少与活性CaMKII的关联的突变驱动突触NR 2B阻止LTP。自发活动驱动的增强显示出类似的结果。我们的结论是，激活CaMKII和NR 2B之间的关联是需要不同形式的突触增强。通常在许多脑区观察到的突触NMDA-R中NR 2B至NR 2A含量的转换可能通过控制活性CaMKII的结合而导致可塑性降低。
Calcium entry through postsynaptic NMDA-Rs and subsequent activation of CaMKII trigger synaptic plasticity in many brain regions. Active CaMKII can bind to NMDA-Rs, but the physiological role of this interaction is not well understood. Here, we test if association between active CaMKII and synaptic NMDA-Rs is required for synaptic plasticity. Switching synaptic NR2B-containing NMDA-Rs that bind CaMKII with high affinity with those containing NR2A, a subunit with low affinity for CaMKII, dramatically reduces LTP. Expression of NR2A with mutations that increase association to active CaMKII recovers LTP. Finally, driving into synapses NR2B with mutations that reduce association to active CaMKII prevents LTP. Spontaneous activity-driven potentiation shows similar results. We conclude that association between active CaMKII and NR2B is required for different forms of synaptic enhancement. The switch from NR2B to NR2A content in synaptic NMDA-Rs normally observed in many brain regions may contribute to reduced plasticity by controlling the binding of active CaMKII.