Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination
Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination
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DOI：
10.1073/pnas.1511513113
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发表时间：
2016-02-23
影响因子：
11.1
通讯作者：
Watanabe, Masahiko
中科院分区：
文献类型：
--
作者：
Ichikawa, Ryoichi;Hashimoto, Kouichi;Watanabe, Masahiko
在小脑浦肯野细胞（PCs）中，一个单一的“赢家”攀爬纤维（CF）独占近端树突，而成千上万的平行纤维（PF）支配远端树突，CF和PF输入都支配一个狭窄的中间区域。目前尚不清楚这种分离的CF和PF神经支配是如何在PC树突上建立的。通过连续电镜重建树突神经支配，我们发现，从出生后9-15天开始，由于重叠神经支配区域的扩大，CF和PF的神经支配区域都在大力扩张。从出生后第15天起，这些区域的分离发生，重叠的近端区域明显缩短。因此，异源输入的神经支配区域在出生后早期被完善。有趣的是，这种转变在缺乏1型代谢性谷氨酸受体（mGluR1）或蛋白激酶C γ (PKC γ)的突变小鼠中被阻止，导致异常扩大的重叠区域持续存在。慢病毒介导的mGluR1 α在mGluR1缺陷的pc中的表达挽救了这种被阻止的区域细化。在获救的PCs近端树突，PF突触被消除，取而代之的是自由棘，而CF突触的数量和密度不变。由于mGluR1-PKC信号通路对于CF突触消除的后期也是必不可少的，因此该信号通路促进了pc中兴奋性突触连接的两个关键特征，即通过消除体细胞中冗余的CF突触来实现CF单神经支配，以及通过消除近端树突中竞争的PF突触来实现CF和PF神经支配的分离。
In Purkinje cells (PCs) of the cerebellum, a single "winner" climbing fiber (CF) monopolizes proximal dendrites, whereas hundreds of thousands of parallel fibers (PFs) innervate distal dendrites, and both CF and PF inputs innervate a narrow intermediate domain. It is unclear how this segregated CF and PF innervation is established on PC dendrites. Through reconstruction of dendritic innervation by serial electron microscopy, we show that from postnatal day 9-15 in mice, both CF and PF innervation territories vigorously expand because of an enlargement of the region of overlapping innervation. From postnatal day 15 onwards, segregation of these territories occurs with robust shortening of the overlapping proximal region. Thus, innervation territories by the heterologous inputs are refined during the early postnatal period. Intriguingly, this transition is arrested in mutant mice lacking the type 1 metabotropic glutamate receptor (mGluR1) or protein kinase C gamma (PKC gamma), resulting in the persistence of an abnormally expanded overlapping region. This arrested territory refinement is rescued by lentivirus-mediated expression of mGluR1 alpha into mGluR1-deficient PCs. At the proximal dendrite of rescued PCs, PF synapses are eliminated and free spines emerge instead, whereas the number and density of CF synapses are unchanged. Because the mGluR1-PKC gamma signaling pathway is also essential for the late-phase of CF synapse elimination, this signaling pathway promotes the two key features of excitatory synaptic wiring in PCs, namely CF monoinnervation by eliminating redundant CF synapses from the soma, and segregated territories of CF and PF innervation by eliminating competing PF synapses from proximal dendrites.