Kieval J Z, Hubert G W, Charara A, Paré J F, Smith Y
Division of Neuroscience, Yerkes Regional Primate Research Center, and Department of Neurology, Emory University, Atlanta, Georgia 30322, USA.
J Neurosci. 2001 Nov 15;21(22):8746-57. doi: 10.1523/JNEUROSCI.21-22-08746.2001.
The localization and functions of kainate receptors (KARs) in the CNS are still poorly known. In the striatum, GluR6/7 and KA2 immunoreactivity is expressed presynaptically in a subpopulation of glutamatergic terminals and postsynaptically in dendrites and spines. The goal of this study was to further characterize the subcellular and subsynaptic localization of kainate receptor subunits in the monkey striatum. Immunoperoxidase data reveal that the relative abundance of GluR6/7- and KA2-immunoreactive terminals is homogeneous throughout the striatum irrespective of the differential degree of striatal degeneration in Huntington's disease. Pre-embedding and post-embedding immunogold data indicate that >70% of the presynaptic or postsynaptic GluR6/7 and KA2 labeling is expressed intracellularly. In material stained with the post-embedding immunogold method, approximately one-third of plasma membrane-bound gold particles labeling in axon terminals and spines is associated with asymmetric synapses, thereby representing synaptic kainate receptor subunits. On the other hand, >60% of the plasma-membrane bound labeling is extrasynaptic. Both GluR6/7 and KA2 labeling in glutamatergic terminals often occurs in clusters of gold particles along the membrane of large vesicular organelles located at various distances from the presynaptic grid. Anterograde labeling from the primary motor cortex or the centromedian thalamic nucleus indicate that both corticostriatal and thalamostriatal terminals express presynaptic GluR6/7 and KA2 immunoreactivity in the postcommissural putamen. In conclusion, these data demonstrate that kainate receptors in the striatum display a pattern of subcellular distribution different from other ionotropic glutamate receptor subtypes, but consistent with their metabotropic-like functions recently shown in the hippocampus.
中枢神经系统中红藻氨酸受体(KARs)的定位和功能仍鲜为人知。在纹状体中,GluR6/7和KA2免疫反应性在谷氨酸能终末的一个亚群中呈突触前表达,在树突和棘中呈突触后表达。本研究的目的是进一步明确红藻氨酸受体亚基在猴纹状体中的亚细胞和突触下定位。免疫过氧化物酶数据显示,无论亨廷顿病纹状体变性程度如何,GluR6/7和KA2免疫反应性终末在整个纹状体中的相对丰度是均匀的。包埋前和包埋后免疫金数据表明,超过70%的突触前或突触后GluR6/7和KA2标记物在细胞内表达。在采用包埋后免疫金法染色的材料中,轴突终末和棘中约三分之一的质膜结合金颗粒标记物与不对称突触相关,从而代表突触红藻氨酸受体亚基。另一方面,超过60%的质膜结合标记物位于突触外。谷氨酸能终末中的GluR6/7和KA2标记物通常出现在位于距突触前网格不同距离的大泡状细胞器膜上的金颗粒簇中。来自初级运动皮层或丘脑中央中核的顺行标记表明,皮质纹状体和丘脑纹状体终末在连合后壳核中均表达突触前GluR6/7和KA2免疫反应性。总之,这些数据表明,纹状体中的红藻氨酸受体表现出一种与其他离子型谷氨酸受体亚型不同的亚细胞分布模式,但与其最近在海马体中显示的类代谢型功能一致。