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首页> 外文期刊>Neuron >A critical role for GluN2B-containing NMDA receptors in cortical development and function.
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A critical role for GluN2B-containing NMDA receptors in cortical development and function.

机译：含GluN2B的NMDA受体在皮质发育和功能中的关键作用。

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摘要

The subunit composition of N-methyl D-aspartate receptors (NMDARs) is tightly regulated during cortical development. NMDARs are initially dominated by GluN2B (NR2B), whereas GluN2A (NR2A) incorporation increases after birth. The function of GluN2B-containing NMDARs during development, however, is incompletely understood. We generated a mouse in which we genetically replaced GluN2B with GluN2A (2B-->2A). Although this manipulation restored NMDAR-mediated currents at glutamatergic synapses, it did not rescue GluN2B loss of function. Protein translation-dependent homeostatic synaptic plasticity is occluded in the absence of GluN2B, and AMPA receptor contribution is enriched at excitatory cortical synapses. Our experiments indicate that specificity of GluN2B-mediated signaling is due to its unique interaction with the protein effector alpha calcium-calmodulin kinase II and the regulation of the mTOR pathway. Homozygous 2B-->2A mice exhibited high rates of lethality, suppressed feeding, and depressed social exploratory behavior. These experiments indicate that GluN2B-containing NMDARs activate unique cellular processes that cannot be rescued by replacement with GluN2A.
机译：N-甲基D-天冬氨酸受体（NMDARs）的亚基组成在皮质发育过程中受到严格调节。 NMDAR最初由GluN2B（NR2B）主导，而GluN2A（NR2A）的掺入在出生后增加。但是，在开发过程中，含GluN2B的NMDAR的功能尚不完全清楚。我们生成了一只小鼠，其中我们用GluN2A（2B-> 2A）遗传取代了GluN2B。尽管此操作恢复了谷氨酸能突触处NMDAR介导的电流，但它不能挽救GluN2B功能丧失。在不存在GluN2B的情况下，蛋白质翻译依赖的稳态突触可塑性被闭塞，并且在兴奋性皮层突触中AMPA受体的贡献得以丰富。我们的实验表明，GluN2B介导的信号传导的特异性是由于其与蛋白质效应因子α钙钙调蛋白激酶II的独特相互作用以及mTOR通路的调节。纯合子2B-> 2A小鼠表现出高致死率，抑制进食和沮丧的社会探索行为。这些实验表明，含GluN2B的NMDAR激活了独特的细胞过程，这些过程无法通过用GluN2A替代来挽救。

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