Flint A C, Maisch U S, Weishaupt J H, Kriegstein A R, Monyer H
Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
J Neurosci. 1997 Apr 1;17(7):2469-76. doi: 10.1523/JNEUROSCI.17-07-02469.1997.
NMDA receptors play important roles in learning and memory and in sculpting neural connections during development. After the period of peak cortical plasticity, NMDA receptor-mediated EPSCs (NMDAR EPSCs) decrease in duration. A likely mechanism for this change in NMDA receptor properties is the molecular alteration of NMDA receptor structure by regulation of NMDA receptor subunit gene expression. The four modulatory NMDAR2A-D (NR2A-D) NMDA receptor subunits are known to alter NMDA receptor properties, and the expression of these subunits is regulated developmentally. It is unclear, however, how the four NR2 subunits are expressed in individual neurons and which NR2 subunits are important to the regulation of NMDA receptor properties during development in vivo. Analysis of NR2 subunit gene expression in single characterized neurons of postnatal neocortex revealed that cells expressing NR2A subunit mRNA had faster NMDAR EPSCs than cells not expressing this subunit, regardless of postnatal age. Expression of NR2A subunit mRNA in cortical neurons at even low levels seemed sufficient to alter the NMDA receptor time course. The proportion of cells expressing NR2A and displaying fast NMDAR EPSCs increased developmentally, thus providing a molecular basis for the developmental change in mean NMDAR EPSC duration.
NMDA受体在学习和记忆以及发育过程中塑造神经连接方面发挥着重要作用。在皮质可塑性达到峰值的时期之后，NMDA受体介导的兴奋性突触后电流（NMDAR EPSCs）的持续时间会缩短。NMDA受体特性发生这种变化的一个可能机制是通过调节NMDA受体亚基基因表达来改变NMDA受体结构的分子变化。已知四种调节性NMDAR2A-D（NR2A-D）NMDA受体亚基会改变NMDA受体特性，并且这些亚基的表达在发育过程中受到调控。然而，尚不清楚这四种NR2亚基在单个神经元中是如何表达的，以及在体内发育过程中哪些NR2亚基对NMDA受体特性的调节很重要。对出生后新皮质单个特征明确的神经元中NR2亚基基因表达的分析表明，无论出生后年龄如何，表达NR2A亚基mRNA的细胞的NMDAR EPSCs比不表达该亚基的细胞更快。即使在皮质神经元中低水平表达NR2A亚基mRNA似乎也足以改变NMDA受体的时间进程。表达NR2A并显示快速NMDAR EPSCs的细胞比例在发育过程中增加，从而为平均NMDAR EPSC持续时间的发育变化提供了分子基础。
