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The Journal of Neuroscience, December 1, 2004, 24(48):10900-10907; doi:10.1523/JNEUROSCI.2240-04.2004

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Cellular/Molecular
Enhanced Inhibitory Synaptic Transmission in the Cerebellar Molecular Layer of the GluR{delta}2 Knock-Out Mouse

Gen Ohtsuki,1,2 Shin-ya Kawaguchi,1,2 Masayoshi Mishina,3 and Tomoo Hirano1,2

1Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan, 2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan, and 3Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, and Solution-Oriented Research for Science and Technology, Tokyo 113-0033, Japan

A novel ionotropic glutamate receptor subunit {delta}2 (GluR{delta}2), which is specifically expressed in cerebellar Purkinje neurons (PNs), is implicated in the induction of long-term depression. Mutant mice deficient in GluR{delta}2 ({delta}2-/-) have abnormal cerebellar synaptic organization and impaired motor coordination and learning. Previous in vivo extracellular recordings in{delta}2-/- revealed that PN activity distinct from that in wild-type (WT) mice is attributable to enhanced climbing fiber activity. Here, we report that GABAergic synaptic transmission was enhanced in the molecular layer of the cerebellar cortex in {delta}2-/-. Optical recordings in cerebellar slice preparations indicated that application of bicuculline, a GABAA receptor antagonist, increased the amplitude and area of excitation propagation more in {delta}2-/- than in WT. Whole-cell patch-clamp recordings from PNs demonstrated that miniature IPSC (mIPSC) amplitude were larger in {delta}2-/- than in WT. Also, rebound potentiation (RP), a type of long-lasting inhibitory synaptic potentiation inducible by postsynaptic depolarization of PNs in WT, was not induced in slices prepared from {delta}2-/-. In contrast, RP was induced in cultured PNs prepared from {delta}2-/-. Pharmacologic activation of climbing fibers in WT in vivo increased mIPSC amplitudes in PNs and prevented RP induction. These results suggest that enhanced climbing fiber activity in {delta}2-/- potentiates IPSC amplitudes in PNs through RP in vivo, resulting in the prevention of additional RP induction.

Key words: cerebellum; Purkinje cell; receptor; glutamate; inhibitory synapse; synaptic plasticity


Received June 9, 2004; revised September 24, 2004; accepted October 18, 2004.




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