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

Abstract

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.

On the resemblance of synapse formation and CNS myelination

“…Importantly, the existence of axon-OPC synapses has been confirmed in vivo (Bergles et al, 2000), but their functions are not yet known. Recently, in addition to calcium-permeable AMPA receptors (Zonouzi et al, 2011), the presence of functional voltage-gated calcium channels in OPCs was confirmed (Haberlandt et al, 2011). These proteins may enable calcium entry following axon-OPC synapse activity and subsequent activation of intracellular signaling cascades.…”

Oligodendrocyte Development and Plasticity

“…Indeed, activation of these NMDA receptors on OPCs can induce changes in the composition and abundance of AMPA receptors (Ge et al 2006). The latter are also modulated by the Cornichon and TARP accessory proteins (Zonouzi et al 2011;Coombs et al 2012), which control the trafficking and kinetics of AMPA receptors in neurons, so axon -OPC synapses appear to have considerable capacity for modification.…”

Glutamate signalling: A multifaceted modulator of oligodendrocyte lineage cells in health and disease

“…Activating OPC mGluRs prompts differentiation (Spampinato et al, 2014;Wake et al, 2011) and regulates AMPA receptor expression (Zonouzi et al, 2011) and calcium influx, mediated by ionotropic glutamate receptors (iGluRs). Calcium influx via iGluRs up-regulates the expression of immediate early genes (Gallo et al, 1996;Lundgaard et al, 2013;Pende et al, 1994), which are associated with the regulation of cell growth and differentiation (Herschman, 1991;McMahon and Monroe, 1992).…”