Tanaka Mika, Yamaguchi Kazuhiko, Tatsukawa Tetsuya, Theis Martin, Willecke Klaus, Itohara Shigeyoshi
RIKEN Brain Science Institute (BSI) Japan.
Front Neurosci. 2008 Dec 15;2(2):225-33. doi: 10.3389/neuro.01.038.2008. eCollection 2008 Dec.
Connexin43 (Cx43), a major component of astrocytic gap junctions, is abundantly expressed in Bergmann glial cells (BGCs) in the cerebellum, but the function of Cx43 in BGCs is largely unknown. BGCs are specialized astrocytes closely associated with Purkinje cells. Here, we review our recent studies of the role of Cx43 in gap junctional coupling between BGCs and in cerebellar function. We generated Cx43 conditional knockout mice with an S100b-Cre transgenic line (Cx43(fl/fl):S100b-Cre), in which there was a significant postnatal loss of Cx43 in BGCs and cerebellar astrocytes. Gap junctional coupling between BGCs measured by dye coupling was virtually abolished in Cx43(fl/fl):S100b-Cre mice. Electrophysiologic and behavioral analyses suggested that Cx43-mediated gap junctions and Cx43 hemichannels in BGCs are not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning. These findings raise questions regarding the regional differences in the impact of the loss of Cx43 in the brain.
连接蛋白43(Cx43)是星形胶质细胞缝隙连接的主要成分,在小脑的伯格曼胶质细胞(BGCs)中大量表达,但Cx43在BGCs中的功能在很大程度上尚不清楚。BGCs是与浦肯野细胞密切相关的特殊星形胶质细胞。在这里,我们回顾了我们最近关于Cx43在BGCs之间的缝隙连接偶联以及小脑功能中的作用的研究。我们用S100b-Cre转基因系生成了Cx43条件性敲除小鼠(Cx43(fl/fl):S100b-Cre),其中BGCs和小脑星形胶质细胞在出生后Cx43显著缺失。通过染料偶联测量的BGCs之间的缝隙连接偶联在Cx43(fl/fl):S100b-Cre小鼠中几乎被消除。电生理和行为分析表明,BGCs中Cx43介导的缝隙连接和Cx43半通道对于小脑依赖性运动协调和运动学习所需的神经元-胶质细胞相互作用不是必需的。这些发现引发了关于大脑中Cx43缺失影响的区域差异的问题。