Corti C, Aldegheri L, Somogyi P, Ferraguti F
Cambridge Brain Bank Laboratory, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Neuroscience. 2002;110(3):403-20. doi: 10.1016/s0306-4522(01)00591-7.
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.
Ⅲ组代谢型谷氨酸受体（mGluRs）可被L-2-氨基-4-膦酰丁酸（L-AP4）选择性激活，L-AP4可使突触传递受到抑制。不同Ⅲ组mGluRs对L-AP4效应的相对贡献仍有待阐明。在此，我们使用针对mGluR4整个C末端结构域产生的亲和纯化抗体，评估了mGluR4在大鼠和小鼠脑中的分布。这些抗体在转染的COS 7细胞中与mGluR4特异性反应，而不与其他mGluRs反应。在mGluR4基因靶向缺失的小鼠脑中未检测到免疫反应性。用于光镜和电镜的包埋前免疫细胞化学显示，在小脑皮质、基底神经节、丘脑的感觉中继核以及一些海马区域标记最为强烈。免疫标记在突触前活性区最为强烈。在基底神经节中，直接和间接纹状体输出通路均显示免疫标记的终末主要在树突干上形成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其作为突触前异受体发挥作用。在小脑皮质和海马中，mGluR4也定位于形成Ⅰ型突触的终末，在那里它可能作为自身受体发挥作用。在海马中，mGluR4标记在齿状分子层以及CA1 - 3层的分子层和腔隙层最为突出。一些腔隙层/肺泡间神经元的树突-体细胞轮廓被mGluR4标记的轴突终末大量装饰，这些终末形成Ⅰ型或Ⅱ型突触。这种差异定位表明通过mGluR4的靶细胞依赖性突触分离对突触传递进行调节。我们的结果表明，与其他Ⅲ组mGluRs一样，突触前mGluR4在支配特定类型神经元的终扣活性区高度富集。此外，还讨论了mGluR4剪接异构体的问题。
