In Vivo Regulation of Oligodendrocyte Precursor Cell Proliferation and Differentiation by the AMPA-Receptor Subunit GluA2
Ting-Jiun Chen,
Bartosz Kula,
Bálint Nagy,
Ruxandra Barzan,
Andrea Gall,
Ingrid Ehrlich,
Maria Kukley
Affiliations
Ting-Jiun Chen
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, 72074 Tübingen, Germany
Bartosz Kula
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, 72074 Tübingen, Germany
Bálint Nagy
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, 72074 Tübingen, Germany; Institute of Science and Technology (IST) Austria, 3400 Klosterneuburg, Austria
Ruxandra Barzan
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, 72074 Tübingen, Germany
Andrea Gall
Learning and Memory Group, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Learning and Memory Group, Hertie Institute for Brain Research, University of Tübingen, 72076 Tübingen, Germany; Department of Neurobiology, IBBS, University of Stuttgart, 70569 Stuttgart, Germany
Ingrid Ehrlich
Learning and Memory Group, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Learning and Memory Group, Hertie Institute for Brain Research, University of Tübingen, 72076 Tübingen, Germany; Department of Neurobiology, IBBS, University of Stuttgart, 70569 Stuttgart, Germany
Maria Kukley
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Department of Ophthalmology, Research Institute of Ophthalmology, Faculty of Medicine, University Hospital Tübingen, 72076 Tübingen, Germany; Corresponding author
Summary: 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: NG2, OPC, oligodendrocytes, myelination, white matter, synaptic, AMPA receptors, glutamate, proliferation, differentiation
