In Vivo Regulation of Oligodendrocyte Precursor Cell Proliferation and Differentiation by the AMPA-Receptor Subunit GluA2

• Published in: Cell reports (Cambridge) 2018-10, Vol.25 (4), p.852-861.e7
• Main Authors: Chen, Ting-Jiun, Kula, Bartosz, Nagy, Bálint, Barzan, Ruxandra, Gall, Andrea, Ehrlich, Ingrid, Kukley, Maria
• Format: Article
• Language: English
• Subjects: AMPA receptors; differentiation; glutamate; myelination; NG2; oligodendrocytes; OPC; proliferation; synaptic; white matter
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.09.066

The functional role of AMPA receptor (AMPAR)-mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GluA2 subunit. Expression of the unedited (Ca2+ permeable) or the pore-dead GluA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes. Expression of the cytoplasmic C-terminal (GluA2(813-862)) of the GluA2 subunit (C-tail), a modification designed to affect the interaction between GluA2 and AMPAR-binding proteins and to perturb trafficking of GluA2-containing AMPARs, decreased the differentiation of OPCs without affecting their proliferation. These findings suggest that ionotropic and non-ionotropic properties of AMPARs in OPCs, as well as specific aspects of AMPAR-mediated signaling at axon-OPC synapses in the mouse corpus callosum, are important for balancing the response of OPCs to proliferation and differentiation cues. [Display omitted] •AMPA receptors (AMPARs) with modified properties are expressed in OPCs in vivo•Channel-pore mutations of AMPARs affect functional properties of axon-OPC synapses•Expression of Ca2+-permeable AMPARs alters proliferation and differentiation of OPCs•Introducing the C-tail of the GluA2 subunit of AMPARs reduces differentiation of OPCs In the brain, oligodendrocyte precursor cells (OPCs) receive glutamatergic AMPA-receptor-mediated synaptic input from neurons. Chen et al. show that modifying AMPA-receptor properties at axon-OPC synapses alters proliferation and differentiation of OPCs. This expands the traditional view of synaptic transmission by suggesting neurons also use synapses to modulate behavior of glia.