Development of NMDA NR2 subunits and their roles in critical period maturation of neocortical GABAergic interneurons.

Development of NMDA NR2 subunits and their roles in critical period maturation of neocortical GABAergic interneurons.
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DOI:
10.1002/dneu.20844
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发表时间:
2011-03
影响因子:
3
通讯作者:
Sun, Qian-Quan
Sun, Qian-Quan
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Zhi;Sun, Qian-Quan

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本研究的目的是:1)测定GABA能中间神经元NMDAR亚基组成在关键期的变化;2)检测长期阻断特定的NR2亚单位对GABA能中间神经元成熟的影响。结果表明:1)CP后组NMDAR介导的EPSCs(EPSCsNMDAR)波幅明显增大。2)前CP组的变异系数(CV)、τ衰减率和EPSCsNMDAR的半宽度均显著大于前CP组。3)后CP组与前CP组的半激活电压左移。4)使用亚基特异性拮抗剂,我们发现NR2的组成在出生后向更多的NR2A介导的EPSCsNMDAR转移。这些变化发生在CP的2天窄窗内,快峰(FS)和规则峰(RSNP)中间神经元之间的变化相似。5)慢性阻断NR2a,但不阻断NR2B,可降低桶状皮质第2/3层和第4层小白蛋白(PV)的表达,但不影响其他钙结合蛋白的表达。6)慢性阻断NR2A选择性地影响FS细胞介导的IPSCs的成熟。综上所述,我们首次报道了CP过程中中间神经元NMDA、NR2亚单位分子组成的发育性变化,以及慢性阻断NR2A而不是NR2B对FS细胞PV表达和抑制性突触传递的影响。这些结果支持了NR2A亚单位在CP时快速放电GABA能神经回路发育可塑性中的重要作用。
The goals of this research are to 1) determine the changes in the composition of NMDA receptor (NMDAR) subunits in GABAergic interneurons during critical period (CP); and 2) test the effect of chronic blockage of specific NR2 subunits on the maturation of specific GABAergic interneurons. Our data demonstrate that: 1) The amplitude of NMDAR mediated EPSCs (EPSCsNMDAR) was significantly larger in the postCP group. 2) The coefficient of variation (CV), τdecay and half-width of EPSCsNMDAR were significantly larger in the preCP group. 3) A leftward shift in the half-activation voltages in the postCP vs. preCP group. 4) Using subunit-specific antagonists, we found a postnatal shift in NR2 composition towards more NR2A mediated EPSCsNMDAR. These changes occurred within a 2-day narrow window of CP and were similar between fast-spiking (FS) and regular spiking (RSNP) interneurons. 5) Chronic blockage of NR2A, but not NR2B, decreased the expression of parvalbumin (PV), but not other calcium binding proteins in layer 2/3 and 4 of barrel cortex. 6) Chronic blockage of NR2A selectively affected the maturation of IPSCs mediated by FS cells. In summary, we have reported, for the first time, developmental changes in the molecular composition of NMDA NR2 subunits in interneurons during CP, and the effects of chronic blockage of NR2A but not NR2B on PV expression and inhibitory synaptic transmission from FS cells. These results support an important role of NR2A subunits in developmental plasticity of fast-spiking GABAergic circuits during CP.
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发表时间: 2000-06-15
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