In vivo regulation of oligodendrocyte precursor cell proliferation and differentiation by AMPA-receptor subunit GluA2

Abstract

Oligodendrocyte precursor cells (OPCs), also known as NG2 cells, are widespread in the grey and white matter regions throughout the entire central nervous system. OPCs express functional 3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) and receive glutamatergic synaptic input from neurons. Transition of OPCs to the pre-myelinating stage is accompanied by the rapid removal of glutamatergic synaptic input, including downregulation of AMPARs. However, the functional role of AMPARs mediated synaptic signaling between neurons and OPCs remains unclear. The goal of my study was to alter the AMPARs mediated signaling between neurons and OPCs in the mouse corpus callosum in vivo, and to study the consequences of these alterations for proliferation and differentiation of OPCs. To reach this goal, I perturbed the properties of GluA2-containing AMPARs in callosal OPCs during the 2-3 postnatal weeks. Expression of Ca2+-permeable or pore-dead GluA2-containing AMPARs altered Ca2+ permeability of AMPARs in OPCs, and resulted in the increased proliferation and reduced differentiation of OPCs. Expression of GluA2 carboxyl-terminus, which is expected to affect the interaction between GluA2 subunit and AMPARs-binding-proteins and to perturb the trafficking of GluA2-containing AMPARs, did not change the Ca2+ permeability of AMPARs but suppressed the differentiation of OPCs into OLs. The results of my study suggest that properties of AMPARs-mediated signaling between neurons and OPCs in the mouse corpus callosum are important for regulation of differentiation and proliferation of OPCs.