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

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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.