Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS
Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS
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DOI：
10.1016/s0306-4522(01)00591-7
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Ferraguti, F
中科院分区：
文献类型：
--
作者：
Corti, C;Aldegheri, L;Ferraguti, F
L-2-氨基-4-磷酸丁酸酯选择性激活代谢型谷氨酸受体，抑制突触传递，但不同类型代谢型谷氨酸受体对L-氨基丁酸酯作用的相对贡献尚不清楚。在这里，我们使用针对mGluR4整个C末端结构域的亲和纯化抗体来评估mGluR4在大鼠和小鼠脑中的分布。在COS 7细胞中，抗体与mGluR4发生特异性反应，而不与其他mGluR发生反应。在mGluR4基因靶向缺失的小鼠的大脑中没有检测到免疫反应。包埋前免疫细胞化学光镜和电子显微镜显示，在小脑皮层、基底节、丘脑感觉中继核和一些海马区标记最强。突触前活动区的免疫标记最强。在基底节，纹状体的直接和间接输出通路都显示免疫标记的终末主要形成树突上的II型突触，mGluR4在纹状体投射神经元的GABA能终末上的定位表明，mGluR4可能是突触前异型受体。在小脑皮层和海马区，mGluR4也定位于建立I型突触的终末，在那里它可能作为自身受体运作。在海马齿状分子层和CA1-3层腔隙分子层和东方核，mGluR4标记的轴突终末被mGluR4标记的轴突终末点缀，形成I型或II型突触。这种差异定位表明，突触传递是通过mGluR4的靶细胞依赖的突触分离来调节的。我们的结果表明，像其他III型mGluR一样，突触前mGluR4在支配特定类型神经元的突触活动区高度丰富。此外，还讨论了mGluR4亚型的选择性剪接问题。(C)2002年IBRO。爱思唯尔科学有限公司出版。版权所有。
Group III metabotropic glutamate receptors (mGluRs) are selectively activated by L-2-amino-4-phosphonobutyrate (L-AP4), which produces depression of synaptic transmission, The relative contribution of different group III mGluRs to the effects of L-AP4 remains to be clarified. Here, we assessed the distribution of mGluR4 in the rat and mouse brain using affinity-purified antibodies raised against its entire C-terminal domain. The antibodies reacted specifically with mGluR4 and not with other mGluRs in transfected COS 7 cells. No immunoreactivity was detected in brains of mice with gene-targeted deletion of mGluR4. Pre-embedding immunocytochemistry for light and electron microscopy showed the most intense labelling in the cerebellar cortex, basal ganglia, the sensory relay nuclei of the thalamus, and some hippocampal areas. Immunolabelling was most intense in presynaptic active zones. In the basal ganglia, both the direct and indirect striatal output pathways showed immunolabelled terminals forming mostly type II synapses on dendritic shafts, The localisation of mGluR4 on GABAergic terminals of striatal projection neurones suggests a role as a presynaptic heteroreceptor. In the cerebellar cortex and hippocampus, mGluR4 was also localised in terminals establishing type I synapses, where it probably operates as an autoreceptor. In the hippocampus, mGluR4 labelling was prominent in the dentate molecular layer and CA1-3 strata lacunosum moleculare and oriens, Somatodendritic profiles of some stratum oriens/alveus interneurones were richly decorated with mGluR4-labelled axon terminals making either type I or II synapses. This differential localisation suggests a regulation of synaptic transmission via a target cell-dependent synaptic segregation of mGluR4.Our results demonstrate that, like other group III mGluRs, presynaptic mGluR4 is highly enriched in the active zone of boutons innervating specific classes of neurones. In addition, the question of alternatively spliced mGluR4 isoforms is discussed. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.