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首页> 外文期刊>Neuron >mGluR5 and NMDA Receptors Drive the Experience- and Activity-Dependent NMDA Receptor NR2B to NR2A Subunit Switch.
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mGluR5 and NMDA Receptors Drive the Experience- and Activity-Dependent NMDA Receptor NR2B to NR2A Subunit Switch.

机译：mGluR5和NMDA受体将依赖于经验和活动的NMDA受体NR2B驱动到NR2A亚基开关。

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摘要

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.
机译：在大脑皮层中，由活动和感官体验驱动，从NR2B到含有NR2A的NMDA受体（NMDAR）发生了发展变化。该亚基开关改变NMDAR功能，影响突触可塑性，其失调与神经系统疾病有关。但是，驱动子单元开关的机制尚不清楚。在这里，我们在海马CA1锥体神经元中显示，由活动剧烈驱动的NR2B向NR2A开关需要激活NMDARs和mGluR5，涉及PLC，Ca（2+）从IP（3）R依赖型存储区释放以及PKC活动。在mGluR5基因敲除小鼠中，CA1中的发育性NR2B-NR2A开关不足。此外，在mGluR5基因敲除小鼠的视觉皮层中，不存在通过视觉体验在体内引起的NR2B-NR2A开关。因此，我们建立了mGluR5和NMDARs是依赖于活性的NR2B-NR2A开关所必需的，并且在体内依赖于NMDAR亚基组成的调节中起着关键作用。

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