Developmental Synaptic Plasticity Section, National Institutes of Health, Bethesda, MD 20892, USA.
Neuron. 2011 Apr 28;70(2):339-51. doi: 10.1016/j.neuron.2011.02.045.
In cerebral cortex there is a developmental switch from NR2B- to NR2A-containing NMDA receptors (NMDARs) driven by activity and sensory experience. This subunit switch alters NMDAR function, influences synaptic plasticity, and its dysregulation is associated with neurological disorders. However, the mechanisms driving the subunit switch are not known. Here, we show in hippocampal CA1 pyramidal neurons that the NR2B to NR2A switch driven acutely by activity requires activation of NMDARs and mGluR5, involves PLC, Ca(2+) release from IP(3)R-dependent stores, and PKC activity. In mGluR5 knockout mice the developmental NR2B-NR2A switch in CA1 is deficient. Moreover, in visual cortex of mGluR5 knockout mice, the NR2B-NR2A switch evoked in vivo by visual experience is absent. Thus, we establish that mGluR5 and NMDARs are required for the activity-dependent NR2B-NR2A switch and play a critical role in experience-dependent regulation of NMDAR subunit composition in vivo.
在大脑皮层中，存在由活动和感觉经验驱动的 NR2B-NMDA 受体（NMDAR）向 NR2A-NMDA 受体的发育性转换。这种亚基转换改变了 NMDAR 的功能，影响了突触可塑性，其失调与神经疾病有关。然而，驱动亚基转换的机制尚不清楚。在这里，我们在海马 CA1 锥体神经元中表明，由活性急性驱动的 NR2B-NR2A 转换需要 NMDAR 和 mGluR5 的激活，涉及 PLC、IP（3）R 依赖性储存的 Ca（2+）释放和 PKC 活性。在 mGluR5 敲除小鼠中，CA1 中的发育性 NR2B-NR2A 转换缺失。此外，在 mGluR5 敲除小鼠的视觉皮层中，由视觉经验在体内引发的 NR2B-NR2A 转换不存在。因此，我们确定 mGluR5 和 NMDAR 是活性依赖性 NR2B-NR2A 转换所必需的，并且在体内 NMDA 受体亚基组成的经验依赖性调节中起着关键作用。
