Dendritic translocation establishes the winner in cerebellar climbing fiber synapse elimination.
Dendritic translocation establishes the winner in cerebellar climbing fiber synapse elimination.
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DOI：
10.1523/jneurosci.4561-12.2013
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发表时间：
2013-05-01
期刊：
影响因子：
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通讯作者：
Nishiyama H
中科院分区：
文献类型：
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作者：
Carrillo J;Nishiyama N;Nishiyama H
在哺乳动物神经系统发育的许多区域，功能性突触回路是通过竞争性消除早期形成的冗余突触而形成的。然而，由于在体内直接观察这种动态细胞过程的技术困难，在大脑中如何通过竞争产生获胜的突触仍然不清楚。本研究采用双光子多色活体成像技术，观察了存活小鼠小脑中多余攀爬纤维（CFs）的竞争性消除。出生时，小脑皮质中的每个浦肯野细胞（PC）受多个CFs的神经支配;额外CFs的活动依赖性消退最终在出生后第21天（P）产生大多数PC的单一神经支配。当多余的CFs被修剪时，CFs的终末场从索马易位到PC的树突。在体时间推移成像显示：1）CF末梢在索马上运动性很强，但在树突上运动性明显降低; 2）只有一个CF能够移位到树突，而它们的竞争者仅限于体周区域; 3）开始树突移位的CF成为赢家。此外，选择性光消融的胜利CF（经历树突易位）逆转了其失去的竞争对手的命运。这些结果表明，树突易位是一个关键的细胞事件，决定了在CF消除的赢家。我们建议，CF终端选择性地稳定在树突上，提供不可逆的竞争活力的第一CF形成树突突触。
In many regions of the developing mammalian nervous system, functional synaptic circuitry is formed by competitive elimination of early-formed redundant synapses. However, how winning synapses emerge through competition remains unclear in the brain owing largely to the technical difficulty of directly observing this dynamic cellular process in vivo. Here, we developed a method of two-photon multi-color vital imaging to observe competitive elimination of supernumerary climbing fibers (CFs) in the cerebellum of live mouse pups. At birth, each Purkinje cell (PC) in the cerebellar cortex is innervated by multiple CFs; an activity-dependent regression of supernumerary CFs ultimately yields a single innervation for most PCs by postnatal day (P) 21. As supernumerary CFs are pruned, the terminal field of CFs translocates from the soma to the dendrites of PCs. In vivo time-lapse imaging of CF elimination revealed that: 1) CF terminals were highly motile on the soma, but their motility was significantly reduced on dendrites, 2) only one CF could translocate to the dendrites whereas their competitors were restricted to perisomatic regions, and 3) the CF that began dendritic translocation became the winner. Moreover, selective photo-ablation of the winning CF (that undergoes dendritic translocation) reversed the fate of its losing competitor. These results indicate that dendritic translocation is a key cellular event that determines the winner during CF elimination. We propose that CF terminals are selectively stabilized on dendrites, providing irreversible competitive vigor to the first CF to form dendritic synapses.