Miyazaki Taisuke, Hashimoto Kouichi, Shin Hee-Sup, Kano Masanobu, Watanabe Masahiko
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
J Neurosci. 2004 Feb 18;24(7):1734-43. doi: 10.1523/JNEUROSCI.4208-03.2004.
Synapse formation depends critically on the competition among inputs of multiple sources to individual neurons. Cerebellar Purkinje cells have highly organized synaptic wiring from two distinct sources of excitatory afferents. Single climbing fibers innervate proximal dendrites of Purkinje cells, whereas numerous parallel fibers converge on their distal dendrites. Here, we demonstrate that the P/Q-type Ca2+ channel alpha1A, a major Ca2+ channel subtype in Purkinje cells, is crucial for this organized synapse formation. In the alpha1A knock-out mouse, many ectopic spines were protruded from proximal dendrites and somata of Purkinje cells. Innervation territory of parallel fibers was expanded proximally to innervate the ectopic spines, whereas that of climbing fibers was regressed to the basal portion of proximal dendrites and somata. Furthermore, multiple climbing fibers consisting of a strong climbing fiber and one or a few weaker climbing fibers, persisted in the majority of Purkinje cells and were cowired to the same somata, proximal dendrites, or both. Therefore, the lack of alpha1A results in the persistence of parallel fibers and surplus climbing fibers, which should normally be expelled from the compartment innervated by the main climbing fiber. These results suggest that a P/Q-type Ca2+ channel alpha1A fuels heterosynaptic competition between climbing fibers and parallel fibers and also fuels homosynaptic competition among multiple climbing fibers. This molecular function facilitates the distal extension of climbing fiber innervation along the dendritic tree of the Purkinje cell and also establishes climbing fiber monoinnervation of individual Purkinje cells.
突触的形成关键取决于多个来源的输入信号对单个神经元的竞争。小脑浦肯野细胞具有来自两种不同兴奋性传入源的高度有序的突触连接。单根攀缘纤维支配浦肯野细胞的近端树突，而众多平行纤维汇聚于其远端树突。在此，我们证明P/Q型Ca2+通道α1A（浦肯野细胞中的一种主要Ca2+通道亚型）对于这种有序的突触形成至关重要。在α1A基因敲除小鼠中，许多异位棘突从浦肯野细胞的近端树突和胞体突出。平行纤维的支配区域向近端扩展以支配异位棘突，而攀缘纤维的支配区域退缩至近端树突和胞体的基部。此外，由一根强攀缘纤维和一根或几根较弱攀缘纤维组成的多根攀缘纤维，在大多数浦肯野细胞中持续存在，并共同连接到同一个胞体、近端树突或两者。因此，α1A的缺失导致平行纤维和多余攀缘纤维的持续存在，而这些通常应被从主要攀缘纤维支配的区域排出。这些结果表明，P/Q型Ca2+通道α1A促进了攀缘纤维和平行纤维之间的异突触竞争，也促进了多根攀缘纤维之间的同突触竞争。这种分子功能促进了攀缘纤维支配沿着浦肯野细胞树突的远端延伸，也建立了单个浦肯野细胞的攀缘纤维单支配。
