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大鼠和猴伏隔核壳部与核心中促代谢型谷氨酸受体1a(mGluR1a)和促代谢型谷氨酸受体5(mGluR5)的亚细胞及突触下定位的比较分析

Comparative analysis of the subcellular and subsynaptic localization of mGluR1a and mGluR5 metabotropic glutamate receptors in the shell and core of the nucleus accumbens in rat and monkey.

作者信息

Mitrano Darlene A, Smith Yoland

机构信息

Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

出版信息

J Comp Neurol. 2007 Feb 1;500(4):788-806. doi: 10.1002/cne.21214.

DOI:10.1002/cne.21214
PMID:17154259
Abstract

Group I metabotropic glutamate receptors (mGluRs) play critical roles in synaptic plasticity and drug addiction. To characterize potential sites whereby these receptors mediate their effects in the ventral striatum, we studied the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the shell and core of the nucleus accumbens in rat and monkey. In both species, group I mGluRs are mainly postsynaptic in dendrites and spines, with rare presynaptic labeling in unmyelinated axons. Minor, yet significant, differences in proportions of specific immunoreactive elements were found between the accumbens shell and the accumbens core in monkey. At the subsynaptic level, significant differences were found in the proportion of plasma membrane-bound mGluR5 labeling between species. In dendrites, spines, and unmyelinated axons, a significantly larger proportion of mGluR5 labeling was bound to the plasma membrane in rats (50-70%) than in monkeys (30-50%). Conversely, mGluR1a displayed the same pattern of immunogold labeling in the two species. Electron microscopic colocalization studies revealed 30% colocalization of mGluR1a and mGluR5 in dendrites and as much as 50-65% in spines in both compartments of the rat accumbens. Both group I mGluRs were significantly expressed in D1-immunoreactive dendritic processes (60-75% colocalization) and spines (30-50%) of striatal projection neurons as well as dendrites of cholinergic (30-70%) and parvalbumin-containing (70-85%) interneurons. These findings highlight the widespread expression of group I mGluRs in projection neurons and interneurons of the shell and core of the nucleus accumbens, providing a solid foundation for regulatory and therapeutic functions of group I mGluRs in reward-related behaviors and drug addiction.

摘要

I 型代谢型谷氨酸受体(mGluRs)在突触可塑性和药物成瘾中发挥着关键作用。为了确定这些受体在腹侧纹状体中介导其作用的潜在位点,我们研究了大鼠和猴子伏隔核壳部和核心中 mGluR1a 和 mGluR5 的亚细胞和突触下定位。在这两个物种中,I 型 mGluRs 主要位于树突和棘的突触后,在无髓轴突中仅有罕见的突触前标记。在猴子的伏隔核壳部和伏隔核核心之间,发现特定免疫反应性元件的比例存在微小但显著的差异。在突触下水平,发现不同物种之间质膜结合的 mGluR5 标记比例存在显著差异。在树突、棘和无髓轴突中,大鼠质膜结合的 mGluR5 标记比例(50-70%)显著高于猴子(30-50%)。相反,mGluR1a 在这两个物种中显示出相同的免疫金标记模式。电子显微镜共定位研究显示,大鼠伏隔核两个区域的树突中 mGluR1a 和 mGluR5 的共定位率为 30%,棘中的共定位率高达 50-65%。I 型 mGluRs 在纹状体投射神经元的 D1 免疫反应性树突突起(共定位率 60-75%)和棘(30-50%)以及胆碱能中间神经元(30-70%)和含小白蛋白中间神经元(70-85%)的树突中均有显著表达。这些发现突出了 I 型 mGluRs 在伏隔核壳部和核心的投射神经元和中间神经元中的广泛表达,为 I 型 mGluRs 在奖励相关行为和药物成瘾中的调节和治疗功能提供了坚实的基础。

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