Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats
Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats
复制标题
DOI：
10.1002/dneu.20375
复制
发表时间：
2007-06
影响因子：
3
通讯作者：
Y. Takagishi;K. Hashimoto;T. Kayahara;Masahiko Watanabe;Hiroyuki Otsuka;A. Mizoguchi;M. Kano;Y. Murata
中科院分区：
文献类型：
--
作者：
Y. Takagishi;K. Hashimoto;T. Kayahara;Masahiko Watanabe;Hiroyuki Otsuka;A. Mizoguchi;M. Kano;Y. Murata
肌球蛋白Va是一种基于肌动蛋白的分子马达，参与细胞器运输和膜运输。在这里，我们通过检查稀释编码肌球蛋白Va突变的稀释神经性（d-n）小鼠和稀释角弓反张（dop）大鼠小脑中浦肯野细胞（PC）的攀爬纤维（CF）神经支配，探索肌球蛋白Va在突触回路形成中的作用。用生物素化葡聚糖胺（BDA）对CF进行顺行标记，发现它们的树枝化程度很差，并且它们的尖端仅延伸到成年d-n小鼠分子层（ML）厚度的一半。使用囊泡谷氨酸转运体2（VGluT 2）特异性免疫组织化学来观察CF突触终末，我们发现在发育期间和成年期，这些终末在d‐n小鼠和dop大鼠中沿着PC的近端树突沿着不像在正常动物中那样。在这些动物中还观察到BDA标记的球状静脉曲张和VGluT 2斑点沿着CF分支的不规则分布。最后，VGluT 2阳性CF终末偶尔位于成人d-n小脑的PC胞体上。这些表型与我们的电生理学发现一致，即成年d-n小鼠中CF介导的兴奋性突触后电流（EPSC）的振幅显著较小，衰减较快，并且发育中的d-n小鼠中多个CF的消退略有延迟。两者合计，我们的研究结果表明，肌球蛋白Va是必不可少的终端CF扩展和适当的树突状领土内的PC CF突触的建立。© 2007 Wiley Periodicals，Inc.开发神经生物学，2007年。
Myosin Va is an actin‐based molecular motor that is involved in organelle transport and membrane trafficking. Here, we explored the role of myosin Va in the formation of synaptic circuitry by examining climbing fiber (CF) innervation of Purkinje cells (PCs) in the cerebella of dilute‐neurological (d‐n) mice and dilute‐opisthotonus (dop) rats that have mutations in dilute‐encoded myosin Va. Anterograde labeling of CFs with biotinylated dextran amine (BDA) revealed that they arborized poorly and that their tips extended only half way through the thickness of the molecular layer (ML) in adult d‐n mice. Using immunohistochemistry specific for vesicular glutamate transporter 2 (VGluT2) to visualize CF synaptic terminals, we found that during development and in adulthood, these terminals did not ascend as far along the proximal shaft dendrites of PCs in d‐n mice and dop rats as they did in normal animals. An irregular distribution of BDA‐labeled bulbous varicosities and VGluT2 spots along CF branches were also noted in these animals. Finally, VGluT2‐positive CF terminals were occasionally localized on the PC somata of adult d‐n cerebella. These phenotypes are consistent with our electrophysiological findings that CF‐mediated excitatory postsynaptic currents (EPSCs) were significantly smaller in amplitude and faster in decay in adult d‐n mice, and that the regression of multiple CFs was slightly delayed in developing d‐n mice. Taken together, our results suggest that myosin Va is essential for terminal CF extension and for the establishment of CF synapses within the proper dendritic territories of PCs. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.