Roles of glutamate receptor δ2 subunit (GluRδ2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development

被引:131
作者
Hashimoto, K
Ichikawa, R
Takechi, H
Inoue, Y
Aiba, A
Sakimura, K
Mishina, M
Hashikawa, T
Konnerth, A
Watanabe, M
Kano, M
机构
[1] Kanazawa Univ, Sch Med, Dept Physiol, Kanazawa, Ishikawa 9208640, Japan
[2] Sapporo Med Univ, Dept Anat, Sapporo, Hokkaido 0608556, Japan
[3] Kyoto Univ, Fac Med, Dept Gerontol, Kyoto 6068507, Japan
[4] Hokkaido Univ, Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan
[5] Kobe Univ, Grad Sch Med, Dept Mol & Cellular Biol, Div Cell Biol, Kobe, Hyogo 6500017, Japan
[6] Niigata Univ, Brain Res Inst, Dept Cellular Neurobiol, Niigata 9518585, Japan
[7] Univ Tokyo, Grad Sch Med, Dept Mol Neurobiol & Pharmacol, Tokyo 1130033, Japan
[8] Japan Sci & Technol Corp, CREST, Tokyo 1130033, Japan
[9] RIKEN, Brain Sci Inst, Lab Neural Architecture, Wako, Saitama 3510198, Japan
[10] Univ Munich, Inst Physiol, D-80802 Munich, Germany
关键词
climbing fiber; parallel fiber; cerebellum; Purkinje cell; synapse; glutamate receptor; postnatal development; mutant mouse;
D O I
10.1523/JNEUROSCI.21-24-09701.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Climbing fiber (CF) synapse formation onto cerebellar Purkinje cells (PCs) is critically dependent on the synaptogenesis from parallel fibers (PFs), the other input to PCs. Previous studies revealed that deletion of the glutamate receptor delta2 subunit (GluR delta2) gene results in persistent multiple CF innervation of PCs with impaired PF synaptogenesis, whereas mutation of the metabotropic glutamate receptor subtype 1 (mGluR1) gene causes multiple CF innervation with normal PF synaptogenesis. We demonstrate that atypical CF-mediated EPSCs (CF-EPSCs) with slow rise times and small amplitudes coexisted with typical CF-EPSCs with fast rise times and large amplitudes in PCs from GluR delta2 mutant cerebellar slices. CF-EPSCs in mGluR1 mutant and wild-type PCs had fast rise times. Atypical slow CF responses of GluR delta2 mutant PCs were associated with voltage-dependent Ca2+ signals that were confined to PC distal dendrites. In the wild-type and mGluR1 mutant PCs, CF-induced Ca2+ signals involved both proximal and distal dendrites. Morphologically, CFs of GluR delta2 mutant mice extended to the superficial regions of the molecular layer, whereas those of wildtype and mGluR1 mutant mice did not innervate the superficial one-fifth of the molecular layer. It is therefore likely that surplus CFs of GluR delta2 mutant mice form ectopic synapses onto distal dendrites, whereas those of wild-type and mGluR1 mutant mice innervate proximal dendrites. These findings suggest that GluR delta2 is required for consolidating PF synapses and restricting CF synapses to the proximal dendrites, whereas the mGluR1-signaling pathway does not affect PF synaptogenesis but is involved in eliminating surplus CF synapses at the proximal dendrites.
引用
收藏
页码:9701 / 9712
页数:12
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