Philpot B D, Weisberg M P, Ramos M S, Sawtell N B, Tang Y P, Tsien J Z, Bear M F
Howard Hughes Medical Institute, Department of Neuroscience, Brown University, Box 1953, Providence, RI 02912, USA.
Neuropharmacology. 2001 Nov;41(6):762-70. doi: 10.1016/s0028-3908(01)00136-8.
The NMDA receptor (NMDAR) is a heteromer comprised of NR1 and NR2 subunits. Mice that overexpress the NR2B subunit exhibit enhanced hippocampal LTP, prolonged NMDAR currents, and improved memory ( Tang et al., 1999). In the current study, we explored visual cortex plasticity and NMDAR function in NR2B overexpressing transgenic mice. Unlike the hippocampus, in vitro synaptic plasticity of the visual cortex was unaltered by NR2B overexpression. Consistent with the plasticity findings, NMDAR excitatory postsynaptic current (EPSC) durations from layer 2/3 pyramidal cells were similar in wild-type (wt) and transgenic (tg) mice. Furthermore, temporal summation of NMDAR EPSCs to 10, 20, and 40 Hz stimulation did not differ between cells from wt and tg mice. Finally, although in situ studies clearly demonstrate overexpression of NR2B mRNA in visual cortex, we failed to observe a significant elevation in the synaptic expression of NR2B protein. We conclude that the synaptic ratio of NR2B over NR2A in the NMDA receptor complex in the visual cortex is not significantly influenced by the transgene overexpression. These data suggest that mRNA availability is not a limiting factor for the synthesis of NR2B protein in the visual cortex, and support the hypothesis that levels of NR2A, rather than NR2B, normally determine the subunit composition of NMDARs in visual cortex.
N-甲基-D-天冬氨酸受体（NMDAR）是一种由NR1和NR2亚基组成的异聚体。过表达NR2B亚基的小鼠表现出海马长时程增强（LTP）增强、NMDAR电流延长以及记忆力改善（Tang等人，1999年）。在本研究中，我们探究了过表达NR2B的转基因小鼠视觉皮层的可塑性和NMDAR功能。与海马体不同，视觉皮层的体外突触可塑性不会因NR2B过表达而改变。与可塑性研究结果一致，野生型（wt）和转基因（tg）小鼠第2/3层锥体细胞的NMDAR兴奋性突触后电流（EPSC）持续时间相似。此外，wt和tg小鼠细胞对10、20和40Hz刺激的NMDAR EPSC时间总和没有差异。最后，尽管原位研究清楚地表明视觉皮层中NR2B mRNA过表达，但我们未能观察到NR2B蛋白的突触表达有显著升高。我们得出结论，视觉皮层NMDA受体复合物中NR2B与NR2A的突触比例不会受到转基因过表达的显著影响。这些数据表明，mRNA可用性不是视觉皮层中NR2B蛋白合成的限制因素，并支持以下假设：正常情况下，NR2A的水平而非NR2B的水平决定了视觉皮层中NMDAR的亚基组成。
