Roles of glutamate receptor δ2 subunit (GluRδ2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development
Roles of glutamate receptor δ2 subunit (GluRδ2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development
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DOI：
10.1523/jneurosci.21-24-09701.2001
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发表时间：
2001-12-15
影响因子：
5.3
通讯作者：
Kano, M
中科院分区：
文献类型：
--
作者：
Hashimoto, K;Ichikawa, R;Kano, M
小脑浦肯野细胞（PC）上爬行纤维（CF）突触的形成主要依赖于平行纤维（PF）的突触发生，PF是PC的另一种输入。先前的研究表明，谷氨酸受体δ 2亚基（GluR δ 2）基因的缺失导致PF突触发生受损的PC的持续性多CF神经支配，而代谢型谷氨酸受体亚型1（mGluR 1）基因的突变导致多CF神经支配与正常PF突触发生。我们证明，非典型CF介导的EPSC（CF-EPSC）与缓慢的上升时间和小振幅共存的典型CF-EPSC与快速上升时间和大振幅的PC从GluR delta 2突变小脑切片。mGluR 1突变体和野生型PC中的CF-EPSC具有快速上升时间。GluR δ 2突变PC的非典型慢CF反应与仅限于PC远端树突的电压依赖性Ca 2+信号相关。在野生型和mGluR 1突变PC中，CF诱导的Ca 2+信号涉及近端和远端树突。从形态学上看，GluR delta 2突变小鼠的CF延伸到分子层的表面区域，而野生型和mGluR 1突变小鼠的CF不支配分子层的表面五分之一。因此，GluR delta 2突变小鼠的多余CF可能在远端树突上形成异位突触，而野生型和mGluR 1突变小鼠的CF支配近端树突。这些研究结果表明，GluR δ 2是巩固PF突触和限制CF突触的近端树突所必需的，而mGluR 1信号通路不影响PF突触，但参与消除过剩的CF突触在近端树突。
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.