Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning
Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning
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DOI：
10.3389/neuro.08.001.2008
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发表时间：
2008-01-01
影响因子：
3
通讯作者：
Itohara, Shigeyoshi
中科院分区：
文献类型：
--
作者：
Tanaka, Mika;Yamaguchi, Kazuhiko;Itohara, Shigeyoshi
Bergmann胶质细胞是小脑中的特化星形胶质细胞。在成熟的小脑分子层中，Bergmann神经胶质突起与浦肯野细胞密切相关，用神经胶质鞘包围浦肯野细胞树突状突触。Bergmann胶质细胞之间存在着强烈的缝隙连接偶联，但其在小脑功能中的意义尚不清楚。缝隙连接蛋白43（Cx43）是星形胶质细胞缝隙连接通道的主要成分，在Bergmann胶质细胞中大量表达。为了研究Cx43介导的Bergmann神经胶质细胞之间的间隙连接在小脑功能中的作用，我们用S100 b-Cre转基因系（Cx43（fl/fl）：S100 b-Cre）产生了Cx43条件性敲除小鼠，其在出生后发病的Bergmann神经胶质细胞和小脑星形胶质细胞中表现出Cx43的显著丧失。Cx43（fl/fl）：S100 b-Cre小鼠具有正常的小脑结构。虽然通过显微注射荧光黄的扩散测量的Bergmann胶质细胞之间的间隙连接偶联在Cx43（fl/fl）：S100 b-Cre小鼠中几乎被废除，电生理学分析显示，小脑长期抑郁症可以诱导和维持正常的小脑切片。此外，在行为水平上，Cx43（fl/fl）：S100 b-Cre小鼠在转棒任务中具有正常的运动协调性和正常的条件眼睑反应。我们的研究结果表明，Cx43介导的Bergmann胶质细胞之间的间隙连接耦合是不必要的小脑依赖的运动协调和运动学习所需的神经元-胶质细胞的相互作用。
Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43), a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43(fl/fl):S100b-Cre), which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43(fl/fl):S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43(fl/fl):S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in their cerebellar slices. In addition, at the behavioral level, Cx43(fl/fl):S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.