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

神经胶质细胞表达多种神经递质受体。值得注意的是，小脑的Bergmann胶质细胞具有Ca^<2+>-渗透性AMPA受体（AMPARs），其组装不含GluR2亚基。为了阐明这些Ca^<2+>-渗透性AMPARs的功能作用，我们通过腺病毒介导的GluR2基因传递将它们转化为Ca^<2+>-不渗透性受体。这种转化使浦肯野细胞树突棘上包裹突触的胶质突收缩，并延缓了突触释放谷氨酸的去除，导致平行纤维和攀爬纤维刺激诱导的EPSCs的衰变期延长。攀爬纤维对浦肯野细胞有多种神经支配作用。因此，胶质细胞Ca^<2+>-可渗透的AMPARs对于Bergmann胶质和谷氨酸突触之间的正常结构和功能关系是必不可少的。为了阐明Ca^<2+>-可渗透AMPARs介导的胶质过程结构变化的分子机制，我们建立了源自大鼠小脑的小脑梭状胶质细胞的单层培养。通过病毒介导的GluR2基因的传递诱导胶质过程的收缩，将Ca^<2+>-渗透性ampar转化为Ca^<2+>-不渗透性受体。相反，Ca^<2+>-可渗透AMPARs的过表达延长了它们。这种胶质延伸在钙调素依赖性蛋白激酶II （CaMKII）的特异性阻滞剂存在下被消除。因此，CaMKII信号通路可能参与了伯格曼胶质过程的这些形态学变化。

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.