Functional roles of Ca^<2+>-permeable AMPA receptors in cerebellar Bergmann glia

小脑伯格曼胶质细胞中Ca^2-通透性AMPA受体的功能作用

• 批准号: 12480246
• 负责人: OZAWA Seiji
• 金额: $ 8.96万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12480246/
• 关键词: Bergmann glia; Cerebellum; AMPA receptor; GluR2; Ca^<2+> permeability; Adenovirus; Glial processes; EPSC; 突起退縮; 突起伸展; シナプス伝達

Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann glial cells in the cerebellum have Ca^<2+>-permeable AMPA receptors (AMPARs) assembled without the GluR2 subunit. To elucidate functional roles of these Ca^<2+>-permeable AMPARs, we converted them into Ca^<2+>-impermeable receptors by adenovirus-mediated delivery of the GluR2 gene. This conversion retracted the glial processes ensheathing synapses on Purkinje cell dendritic spines and retarded the removal of synaptically released glutamate, leading to the prolongation of the decay phase of EPSCs induced by stimulation of parallel and climbing fibers. Furthermore, it caused multiple innervation of Purkinje cells by the climbing fibers. Thus, the glial Ca^<2+>-permeable AMPARs are indispensable for proper structural and functional relations between Bergmann glia and glutamatergic synapses.To elucidate the molecular mechanism underlying the structural changes of glial processes mediated by Ca^<2+>-permeable AMPARs, we established the monolayer culture of cerebellar fusiform glial cells derived from rat cerebellum. Converting Ca^<2+>-permeable AMPARs into Ca^<2+>-impermeable receptors by viral-mediated delivery of GluR2 gene induced retraction of glial processes. In contrast, over-expression of Ca^<2+>-permeable AMPARs elongated them. This glial extension was abolished in the presence of the specific blocker of calmodulin-dependent protein kinase II (CaMKII). It is therefore likely that the CaMKII signaling pathway is involved in these morphological changes in Bergmann glial processes.

神经胶质细胞表达多种神经递质受体。值得注意的是，小脑中的Bergmann神经胶质细胞具有不含GluR2亚基的Ca^2+渗透性AMPA受体（AMPAR）。为了阐明这些Ca^<2+>可渗透的AMPAR的功能作用，我们通过腺病毒介导的GluR 2基因递送将它们转化为Ca^<2+>不可渗透的受体。这种转换回神经胶质过程鞘突触浦肯野细胞树突棘和延迟突触释放的谷氨酸的清除，导致延长的衰减阶段的刺激诱导的平行和攀爬纤维的EPSC。此外，它引起了多个神经支配的浦肯野细胞的攀缘纤维。因此，胶质细胞Ca^<2+>渗透性AMPAR是Bergmann胶质细胞与突触之间正确的结构和功能关系所不可或缺的，为了阐明Ca^<2+>渗透性AMPAR介导的胶质细胞结构变化的分子机制，我们建立了大鼠小脑梭形胶质细胞的单层培养。通过病毒介导的GluR2基因的传递将Ca^<2 +>可渗透的AMPAR转化为Ca^<2+>不可渗透的受体诱导神经胶质突起的收缩相比之下，Ca^<2+>可渗透的AMPAR的过度表达延长了它们。这种胶质细胞的延伸被废除的钙调蛋白依赖性蛋白激酶II（CaMKII）的特异性阻断剂的存在下。因此，CaMKII信号通路可能参与Bergmann神经胶质过程中的这些形态学变化。

项目成果

Ozawa, S., et al.: "Responses : Glial processes are glued to synapses via Ca^<2+>-permeable glutamate receptors"Trends in Neurosciences. 25. 7 (2002)

Ozawa, S.等人：“反应：神经胶质细胞过程通过Ca 2+ -渗透性谷氨酸受体粘附到突触”神经科学趋势。

Ishiuchi,S. et al.: "Extension of glial processes by activation of Ca^<2+>-permeable AMPA receptor channels"NeuroReport. (in press).

石内，S.

Iino, M., et al.: "Glia-synapse interaction through Ca^<2+> permeable AMPA receptors in Bergmann glia"Science. 292. 926-929 (2001)

Iino，M.，等人：“伯格曼神经胶质中通过Ca 2+ 渗透性AMPA受体的神经胶质-突触相互作用”《科学》。

Iino, M. et al.: "Glia-synapse interaction through Ca^<2+>-permeable AMPA receptors in Bergmann glia"Science. 292. 926-929 (2001)

Iino，M.等人：“伯格曼神经胶质细胞中通过Ca 2+ -可渗透的AMPA受体的神经胶质细胞突触相互作用”《科学》。

Ishiuchi, S. et al.: "Extension of glial processes by activation of Ca^<2+>-permeable AMPA receptor channels"NeuroReport. 12. 745-748 (2001)

Ishiuchi，S.等人：“通过激活Ca 2+ -可渗透的AMPA受体通道来延长神经胶质过程”NeuroReport。