Roles of Glutamatergic Synaptic Transmission in Synapse Formation of Cerebellar Purkinje Cells, as Revealed by Morphological and Electrophysiological Analyses with Gene Knockout Mice.

GluRdelta2是浦肯野细胞（PC）特异性的嗜离子性谷氨酸受体亚基，而mGluR1是浦肯野细胞（PC）显性的代谢性谷氨酸受体。众所周知，这两种分子在诱导长期抑郁（LTD）中都很重要，长期抑郁是运动学习背后的突触可塑性的一种形式。在本研究项目中，我分析了GluRdelta2和mGluR1基因缺失的敲除小鼠的小脑，以阐明它们在PC突触发育中的作用。连续电镜检查显示，GluRdelta2-KO小鼠出现无突触接触的PC树突棘，导致平行纤维突触减少近一半。相比之下，野生型对照组的所有PC棘均与平行纤维终端接触，在mGluR1-KO小鼠中，PC远端树突上正常形成平行纤维突触。然而，mGluR1-KO小鼠脑干下榄核轴突的攀爬纤维的多神经支配仍然存在。这些结果表明，GluRdelta2在稳定和加强平行纤维和PCs之间的突触连接中起重要作用，而mGluR1则参与消除多余的攀爬纤维。因此，这两种谷氨酸受体在PC突触发育中发挥着不同但重要的作用，就像它们在成熟阶段诱导LTD一样。

The GluRdelta2 is a Purkinje cell (PC)-speciflc ionotropic glutamate receptor subunit, and the mGluR1 is a PC-predominant metabotropic glutamate receptor. Both molecules are known to be important in the induction of long-term depression (LTD), a form of synaptic plasticity underlying the motor learning. In the present research project, I analyzed the cerebellum of knockout mice deficient in the GluRdelta2 and mGluR1, to elucidate their roles in PC synapse development. Serial electron microscopic examination revealed that PC dendritic spines free of synaptic contact emerged in the GluRdelta2-KO mouse, resulting in the reduction of parallel fiber synapses to nearly a half level. By contrast, all PC spines examined in the wild-type control were contacted with parallel fiber terminals, In the mGluR1-KO mouse, parallel fiber synapses were normally formed on distal PC dendrites. However, multiple innervation by climbing fibers, axons from brainstem inferior olivary nucleus, persisted in the mGluR1-KO mouse. These results suggest that GluRdelta2 is important in the stabilization and strengthening of synaptic connectivity between parallel fibers and PCs, whereas mGluR1 is involved in the elimination of supernumerary climbing fibers. Therefore, the two glutamate receptors play distinct, but essential roles in the PC synapse development, as they do in the induction of LTD at mature stages.