Organization of NMDA receptors at extrasynaptic locations.
Organization of NMDA receptors at extrasynaptic locations.
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DOI：
10.1016/j.neuroscience.2010.01.022
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发表时间：
2010-04-28
期刊：
影响因子：
3.3
通讯作者：
Wenthold, R. J.
中科院分区：
文献类型：
--
作者：
Petralia, R. S.;Wang, Y. X.;Hua, F.;Yi, Z.;Zhou, A.;Ge, L.;Stephenson, F. A.;Wenthold, R. J.
NMDA 受体存在于神经元的突触和突触外位置。突触外位置的特征很少。在这里，我们使用包埋前免疫过氧化物酶和包埋后免疫金电子显微镜和荧光显微镜来表征体外分离海马神经元以及体内成人和出生后海马中突触外 NMDA 受体的位置。我们发现体内和体外神经元上的突触外NMDA受体通常集中在与相邻突的接触点，这些突主要是轴突、轴突末端或神经胶质细胞。许多这些接触被证明含有粘附因子，例如钙粘蛋白和连环蛋白。我们还发现突触外 NMDA 受体与 MAGUK、PSD-95 和 SAP102 之间的关联。还观察到发育差异。在体内出生后第2天，通常可以在具有不同密度的位点发现突触外NMDA受体，而在体内成年海马的突触外NMDA受体位点很少看到致密物质。这种差异可能表明出生后早期突触外 NMDA 受体的许多位点代表突触形成或可能是突触消除的位点。正如体内和体外研究所表明的，在所有年龄段，树突或棘侧面的突触外 NMDA 受体可能与其他蛋白质形成复合物，在许多情况下，与相邻细胞过程稳定关联。这些关联可能促进突触外 NMDA 受体的独特功能。
NMDA receptors are found in neurons both at synapses and in extrasynaptic locations. Extrasynaptic locations are poorly characterized. Here we used preembedding immunoperoxidase and postembedding immunogold electron microscopy and fluorescence light microscopy to characterize extrasynaptic NMDA receptor locations in dissociated hippocampal neurons in vitro and in the adult and postnatal hippocampus in vivo. We found that extrasynaptic NMDA receptors on neurons in vivo and in vitro were usually concentrated at points of contact with adjacent processes, which were mainly axons, axon terminals, or glia. Many of these contacts were shown to contain adhesion factors such as cadherin and catenin. We also found associations of extrasynaptic NMDA receptors with the MAGUKs, PSD-95 and SAP102. Developmental differences were also observed. At postnatal day 2 in vivo, extrasynaptic NMDA receptors could often be found at sites with distinct densities whereas dense material was seen only rarely at sites of extrasynaptic NMDA receptors in the adult hippocampus in vivo. This difference probably indicates that many sites of extrasynaptic NMDA receptors in early postnatal ages represent synapse formation or possibly sites for synapse elimination. At all ages, as suggested in both in vivo and in vitro studies, extrasynaptic NMDA receptors on dendrites or the sides of spines may form complexes with other proteins, in many cases, at stable associations with adjacent cell processes. These associations may facilitate unique functions for extrasynaptic NMDA receptors.
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