In Vivo regulation of Oligodendrocyte processor cell proliferation and differentiation by the AMPA-receptor Subunit GluA2 Journal Article

Author(s): Chen, Ting J; Kula, Bartosz; Nagy, Balint; Barzan, Ruxandra; Gall, Andrea; Ehrlich, Ingrid; Kukley, Maria L
Article Title: In Vivo regulation of Oligodendrocyte processor cell proliferation and differentiation by the AMPA-receptor Subunit GluA2
Affiliation IST Austria
Abstract: 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. 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.
Keywords: Differentiation; Proliferation; Oligodendrocytes; Glutamate; AMPA receptors; Myelination; NG2; OPC; Synaptic; White matter
Journal Title: Cell Reports
Volume: 25
Issue 4
ISSN: 22111247
Publisher: Elsevier  
Date Published: 2018-10-23
Start Page: 852
End Page: 861.e7
Copyright Statement: CC BY 4.0
DOI: 10.1016/j.celrep.2018.09.066
Notes: This work was supported by Deutsche Forschungsgemeinschaft (DFG) grant KU2569/1-1 (to M.K.); DFG project EXC307Centre for Integrative Neuroscience (CIN), including grant Pool Project 2011-12 (jointly to M.K. and I.E.); and the Charitable Hertie Foundation (to I.E.). CIN is an Excellence Cluster funded by the DFG within the framework of the Excellence Initiative for 2008–2018. M.K. is supported by the Tistou & Charlotte Kerstan Foundation.
Open access: yes (OA journal)