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Calcium Signaling and Cerebellar Synaptic Circuit Development

钙信号传导和小脑突触回路开发

基本信息

批准号：
15016001
负责人：
WATANABE Masahiko
金额：
$ 22.14万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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 Ca^<2+> channel a1A, a major Ca^<2+> channel subtype in Purkinje cells, is crucial for this organized synapse formation. In the alA knockout mouse, ectopic spine formation was frequently observed in proximal dendrites and somata of Purkinje cells. Innervation territory of parallel fibers was expanded proximally to innervate these 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 ones, persisted in the majority of Purkinje cells and were co-wired to the basal somatodendritic domain. The lack of alA, therefore, results in the survival of parallel fibers and surplus climbing fibers, which should normally be expelled from the compartment innervated by the main climbing fiber. We conclude that a P/Q-type Ca^<2+> channel alA fuels both heterosynaptic competition between climbing fibers and parallel fibers and homosynaptic competition among multiple climbing fibers. This molecular function facilitates the distal extension of climbing fiber innervation along Purkinje cell's dendritic tree and also establishes mono climbing fiber innervation of individual Purkinje cells.

突触的形成在很大程度上依赖于不同来源的神经元输入之间的竞争。小脑浦肯野细胞有来自两个不同来源的兴奋性传入的高度组织化的突触连接。浦肯野细胞近端的树突分布着单一的爬行纤维，而远侧的树突上聚集着大量平行的纤维。在这里，我们证明了P/Q型钙通道A1a是浦肯野细胞中主要的钙通道亚型，对于这种有组织的突触形成是至关重要的。在ALA基因敲除小鼠中，异位棘突形成常见于浦肯野细胞的近端树突和胞体。平行纤维的神经支配区域向近端扩展，以支配这些异位棘突，而爬行纤维的神经支配区域退缩到近端树突和体细胞的基底部。此外，在大多数浦肯野细胞中存在着多条攀援纤维，其中包括一根较强的攀援纤维和一根或几根较弱的攀援纤维，并与基本的躯体树突域相连。因此，缺乏ALA导致平行纤维和多余的攀援纤维存活，而这些纤维通常应该从主要攀援纤维所支配的隔室中排出。我们的结论是，P/Q型钙通道ALA既促进了攀爬纤维与平行纤维之间的异突触竞争，也助长了多个攀爬纤维之间的同突竞争。这一分子功能促进了攀爬纤维神经沿着浦肯野细胞树的远端延伸，也建立了单个浦肯野细胞的单一攀援纤维神经支配。