Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNS
Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNS
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DOI：
10.1113/jphysiol.2007.147652
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发表时间：
2008-05-15
影响因子：
5.5
通讯作者：
Manabe, Toshiya
中科院分区：
文献类型：
--
作者：
Miwa, Hideki;Fukaya, Masahiro;Manabe, Toshiya
NMDA型谷氨酸受体是一种异聚体复合物，由NR 1和至少一个NR 2亚基组成。从NR 2B到NR 2A亚基的转换被认为是突触成熟过程中NMDA受体功能改变的基础，并且通常认为它导致NR 2A亚基优先定位在突触位点上，而NR 2B亚基优先定位在成熟脑中的细胞外位点上。也有人提出NR 2A和NR 2B亚基的激活分别导致长时程增强（LTP）和长时程抑制（LTD）。此外，最近的报告表明，突触和突触外受体可能有不同的作用，在突触可塑性，以及在基因表达与神经元死亡。在这里，我们已经调查了是否NR 2B亚单位的受体存在和功能在成熟的突触在杏仁核（LA）和海马CA 1区的外侧核，比较它们的两个大脑区域之间的属性。我们发现，与上述假设相反，NR 2B亚基显著有助于突触传递以及LTP诱导。此外，它的贡献是更大的LA比在CA 1区，和NMDA受体的生物物理特性和NR 2B/NR 2A的比例是不同的两个脑区之间。这些结果表明，含有NR 2B亚基的NMDA受体聚集在突触部位，并负责杏仁核中突触功能和可塑性的独特性质。
The NMDA-type glutamate receptor is a heteromeric complex composed of the NR1 and at least one of the NR2 subunits. Switching from the NR2B to the NR2A subunit is thought to underlie functional alteration of the NMDA receptor during synaptic maturation, and it is generally believed that it results in preferential localization of NR2A subunits on the synaptic site and that of NR2B subunits on the extracellular site in the mature brain. It has also been proposed that activation of the NR2A and NR2B subunits results in long-term potentiation (LTP) and long-term depression (LTD), respectively. Furthermore, recent reports suggest that synaptic and extrasynaptic receptors may have distinct roles in synaptic plasticity as well as in gene expression associated with neuronal death. Here, we have investigated whether NR2B subunit-containing receptors are present and functional at mature synapses in the lateral nucleus of the amygdala (LA) and the CA1 region of the hippocampus, comparing their properties between the two brain regions. We have found, in contrast to the above hypotheses, that the NR2B subunit significantly contributes to synaptic transmission as well as LTP induction. Furthermore, its contribution is greater in the LA than in the CA1 region, and biophysical properties of NMDA receptors and the NR2B/NR2A ratio are different between the two brain regions. These results indicate that NR2B subunit-containing NMDA receptors accumulate on the synaptic site and are responsible for the unique properties of synaptic function and plasticity in the amygdala.