Bidirectional plasticity of calcium-permeable AMPA receptors in oligodendrocyte lineage cells

Oligodendrocyte precursor cells (OPCs), a major glial cell type giving rise to myelinating oligodendrocytes in the CNS, express calcium-permeable (CP-) AMPARs. Although CP-AMPARs are important in OPC proliferation and neuron-glia signalling, they render OPCs susceptible to ischemic damage in early development. Here we identify factors controlling dynamic regulation of AMPAR subtypes in OPCs from rat optic nerve and mouse cerebellar cortex. We find that activation of group 1 mGluRs drives an increase in the proportion of CP-AMPARs, reflected in increased single-channel conductance and inward rectification. This plasticity requires elevation of intracellular calcium, utilizes PI3 kinase, PICK-1 and the JNK pathway. In white matter, neurons and astrocytes release both ATP and glutamate. Surprisingly, activation of purinergic receptors in OPCs decreases CP-AMPAR expression, suggesting a capacity for homeostatic regulation. Finally, we show that stargazin-related transmembrane AMPAR regulatory proteins, which are key for AMPAR surface expression in neurons, regulate CP-AMPAR plasticity in OPCs.