Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Cells. 2022 Jun 23;11(13):2004. doi: 10.3390/cells11132004.
Group I metabotropic glutamate receptors (mGluRs) include mGluR1 and mGluR5, which are coupled to the Gq family of heterotrimeric G-proteins and readily activated by their selective agonist 3,5-dihydroxyphenilglycine (DHPG). mGluR1 and mGluR5 exhibit nearly complementary distributions spatially or temporally in the central nervous system (CNS). In adult cerebellar Purkinje cells (PCs), mGluR1 is a dominant group I mGluR and mGluR5 is undetectable. mGluR1 expression increases substantially during the first three weeks of postnatal development and remains high throughout adulthood. On the other hand, mGluR5 expression is observed during the first two postnatal weeks and then decreases. However, functional differences between mGluR1 and mGluR5 in the CNS remains to be elucidated. To address this issue, we generated "mGluR5-rescue" mice in which mGluR5 is specifically expressed in PCs in global mGluR1-knockout (KO) mice. mGluR5-rescue mice exhibited apparently normal motor coordination, developmental elimination of redundant climbing fiber (CF)-PC synapses, and delay eyeblink conditioning, which were severely impaired in mGluR1-KO mice. We concluded that mGluR5 is functionally comparable with mGluR1 in cerebellar PCs.
I 型代谢型谷氨酸受体（mGluRs）包括 mGluR1 和 mGluR5，它们与 Gq 家族异源三聚体 G 蛋白偶联，容易被其选择性激动剂 3,5-二羟基苯丙氨酸（DHPG）激活。mGluR1 和 mGluR5 在中枢神经系统（CNS）中的空间或时间分布上几乎互补。在成年小脑浦肯野细胞（PCs）中，mGluR1 是主要的 I 型 mGluR，而 mGluR5 则无法检测到。mGluR1 的表达在出生后三周内显著增加，并在整个成年期保持高水平。另一方面，mGluR5 的表达在出生后的前两周观察到，然后减少。然而，中枢神经系统中 mGluR1 和 mGluR5 的功能差异仍有待阐明。为了解决这个问题，我们在全局 mGluR1 敲除（KO）小鼠中生成了“mGluR5 挽救”小鼠，其中 mGluR5 特异性表达在 PCs 中。mGluR5 挽救小鼠表现出明显正常的运动协调、冗余 climbing fiber（CF）-PC 突触的发育消除以及眨眼条件反射的延迟，而这些在 mGluR1-KO 小鼠中严重受损。我们得出结论，mGluR5 在小脑 PCs 中与 mGluR1 具有功能可比性。
