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

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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.