Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression
Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression
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DOI：
10.1186/1756-6606-4-41
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发表时间：
2011-11-15
期刊：
影响因子：
3.6
通讯作者：
Wang, Yu Tian
中科院分区：
文献类型：
--
作者：
Bartlett, Thomas E.;Lu, Jie;Wang, Yu Tian
背景资料：N-甲基-D-天冬氨酸（NMDA）受体的不同GluN 2亚基对诱导双向海马突触可塑性的贡献是一个有争议的话题。作为支持和反驳的证据，亚基专业化的可塑性相反的方向的假设已经积累了，因为它是第一次提出几年前，我们假设，实验条件的差异可能在一定程度上促成了一些不一致的结果，从这些研究。在这里，我们调查了有争议的假设，即长期抑郁症（LTD）是优先诱导的谷氨酸2B含有NMDA受体在CA 1区的海马脑片。我们发现，在矢状方向制备的来自2-3周龄大鼠的脑切片具有GluN 2B非依赖性LTD，而在冠状方向制备的切片具有GluN 2B-依赖性LTD。在对GluN 2B选择性拮抗剂敏感的NMDAR EPSC部分的取向之间没有差异，这使我们相信NMDAR的细胞内信号传导性质在两种制剂中是不同的。冠状切片与矢状切片相比，LTD相关细胞内信号蛋白RasGRF 1与GluN 2B的相关性更大。在矢状面，毒蕈碱型乙酰胆碱受体（mAChRs）的拮抗作用使LTD恢复为GluN 2B依赖的形式，并增加了GluN 2B与RasGRF 1的结合。结论：这些结果提示mAChRs对NMDAR的调节是一种新的形式，并澄清了文献中的一些分歧。
Background: The contribution of different GluN2 subunits of the N-methyl D-aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices.Results: We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B-selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1.Conclusions: These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature.