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

GluRdelta 2是浦肯野细胞（PC）特异性离子型谷氨酸受体亚基，mGluR 1是PC主导的代谢型谷氨酸受体。已知这两种分子在诱导长期抑郁（LTD）中是重要的，长期抑郁是运动学习基础上的一种突触可塑性形式。在本研究项目中，我分析了GluRdelta 2和mGluR 1基因敲除小鼠的小脑，以阐明它们在PC突触发育中的作用。连续电镜检查显示，在GluRdelta 2-KO小鼠中出现了无突触接触的PC树突棘，导致平行纤维突触减少到近一半的水平。相比之下，在野生型对照中检查的所有PC棘与平行纤维末端接触。在mGluR 1-KO小鼠中，平行纤维突触通常在远端PC树突上形成。然而，mGluR 1-KO小鼠中存在由脑干下橄榄核的攀爬纤维和轴突引起的多个神经支配。这些结果表明，GluRdelta 2是重要的平行纤维和PC之间的突触连接的稳定和加强，而mGluR 1参与消除多余的攀爬纤维。因此，这两种谷氨酸受体在PC突触发育中起着不同但必不可少的作用，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.