Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the monkey subthalamic nucleus

Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the monkey subthalamic nucleus
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DOI:
10.1002/cne.20158
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发表时间:
2004-07-05
影响因子:
2.5
通讯作者:
Smith, Y
Smith, Y
中科院分区:
医学3区
文献类型:
--
作者:
Kuwajima, M;Hall, RA;Smith, Y

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I组代谢型谷氨酸受体的两种亚型mGluR1和mGluR5在丘脑底核(subthalamic nucleus,STN)的神经元中突触后表达,它们的激活诱导不同的生理反应。为了测试这些影响是否可以解释的差异定位的两个组I mGluRs,我们分析了亚细胞和亚突触分布的mGluR1a和mGluR5在猴脑。双免疫荧光和光学显微镜分析显示,两组I mGluR亚型强烈共表达的神经元和神经元胞体。星形胶质细胞胞体表现出强烈的mGluR1a,但没有检测到mGluR5,免疫反应。在电子显微镜水平,免疫过氧化物酶标记mGluR1a和mGluR5主要定位在树突。一个显着的比例占总池的mGluR1a免疫反应性元素的胶质细胞的过程,而胶质细胞标记的mGluR5免疫染色切片中遇到的要少得多。预包埋免疫金标记的mGluR树突显示,60 - 70%的金标记的两种mGluR亚型是细胞内,而30 - 40%是apposed到质膜。在质膜并置颗粒中,超过90%是突触外的;少于10%与对称或不对称突触相关。大多数的突触相关的标签被发现在边缘的不对称和对称的突触后专业化。一些突触外的金颗粒聚集在部分质膜紧密贴壁的胶质细胞的过程。这些研究结果表明,mGluR1a和mGluR5表现出类似的模式,在猴海马神经元的突触下定位,两种受体亚型表现出大量的突触外和突触周的定位。(C)2004 Wiley-Liss,Inc.
Both subtypes of group I metabotropic glutamate receptor, mGluR1 and mGluR5, are expressed postsynaptically in neurons of the subthalamic nucleus (STN), and their activation induces different physiological responses. To test whether these effects could be explained by a differential localization of the two group I mGluRs, we analyzed the subcellular and subsynaptic distribution of mGluR1a and mGluR5 in the monkey STN. Double-immunofluorescence and light microscopic analyses revealed that both group I mGluR subtypes were strongly coexpressed in the neuropil and neuronal perikarya. Astrocytic perikarya exhibited intense mGluR1a, but no detectable mGluR5, immunoreactivity. At the electron microscopic level, immunoperoxidase labeling for both mGluR1a and mGluR5 was localized mainly in dendrites. A significant proportion of the total pool of mGluR1a-immunoreactive elements was accounted for by glial cell processes, whereas glial cell labeling was much less frequently encountered in sections immunostained for mGluR5. Preembedding immunogold labeling in STN dendrites revealed that 60-70% of the gold labeling for both mGluR subtypes was intracellular, whereas 30-40% was apposed to the plasma membrane. Of the plasma membrane-apposed particles, more than 90% were extrasynaptic; fewer than 10% were associated with symmetric or asymmetric synapses. Most of the synapse-associated labeling was found at the edges of both asymmetric and symmetric postsynaptic specializations. Some extrasynaptic gold particles were aggregated on parts of the plasma membrane tightly apposed by glial processes. These findings demonstrate that mGluR1a and mGluR5 exhibit a similar pattern of subsynaptic localization in monkey STN neurons, with both receptor subtypes exhibiting substantial extrasynaptic and perisynaptic localization. (C) 2004 Wiley-Liss, Inc.