Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses
Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses
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DOI：
10.1523/jneurosci.20-16-05899.2000
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发表时间：
2000-08-15
影响因子：
5.3
通讯作者：
Cull-Candy, S
中科院分区：
文献类型：
--
作者：
Cathala, L;Misra, C;Cull-Candy, S
在小脑发育过程中，颗粒细胞表现出明显的NMDAR NR2亚基表达的变化，在成熟细胞中从NR2B转变为NR2A和NR2C。尽管各种研究，包括对缺失一个或多个NR2亚基类型的突变小鼠的实验，表明NR2A、NR2B和NR2C亚基对突触NMDAR有贡献，但苔藓纤维EPSC在发育过程中的特性变化尚未得到充分评估。特别是，关于NMDAR EPSCs在成熟动物中的信息缺乏。我们研究了NMDAR在苔藓纤维颗粒细胞突触从形成到成熟的药理学和动力学特性[出生后第7天(P7)-P40大鼠]。诱发的EPSC的非NMDAR和NMDAR介导性成分的相对幅度以及后者的衰变动力学发生了显著变化。NMDA/Non-NMDA比值在P7、P21和P40时相似，但在P12有一个明显的峰值。这一变化与NMDAR EPSC的加速衰退相一致，并伴随着对选择性NR2B拮抗剂异芬普地尔敏感性的降低。到P21时，NMDAR EPSC对镁离子的敏感性大约是P12时的三倍(IC50，76vs28muM)，这表明NR2C亚单位的加入。然而，预测的衰变动力学减慢到更具NR2C失活特征的值，直到第40页才能看到。我们的数据与已知的出生后两周内从NR2B亚基到NR2A亚基的转换是一致的，但表明NR2C亚基的逐渐加入改变了对镁的敏感性，并只在后来影响了EPSC的动力学。
During cerebellar development, granule cells display well characterized changes in the expression of NMDA receptor (NMDAR) NR2 subunits, switching from NR2B to NR2A and NR2C in mature cells. Although various studies, including experiments on mutant mice with one or more NR2 subunit types deleted, suggest that NR2A, NR2B, and NR2C subunits contribute to synaptic NMDARs, changes in the properties of the mossy fiber EPSC during development have not been fully evaluated. In particular, information on NMDAR EPSCs in mature animals is lacking. We have examined pharmacological and kinetic properties of NMDARs at mossy fiber-granule cell synapses from their formation to maturity [postnatal day 7 (P7)-P40 rats]. Significant changes were seen in the relative amplitudes of the non-NMDAR- and NMDAR-mediated components of the evoked EPSC and in the decay kinetics of the latter. The NMDA/non-NMDA ratio was similar at P7, P21, and P40, but showed a clear peak at P12. This change coincided with a speeding of the NMDAR EPSC decay, accompanied by a decrease in sensitivity to ifenprodil (selective NR2B-antagonist). By P21, sensitivity of the NMDAR EPSC to Mg2+ was approximately threefold less than that at P12 (IC50, 76 vs 28 mu M), suggesting incorporation of the NR2C subunit. However, the predicted slowing of decay kinetics to a value more characteristic of NR2C deactivation, was not seen until P40. Our data are consistent with the known switch from NR2B to NR2A subunits during the first two postnatal weeks, but suggest a gradual incorporation of the NR2C subunit that modifies Mg2+ sensitivity and only later influences EPSC kinetics.