title: NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination.
abstract: Oligodendrocyte precursor cells (OPCs) express NMDA receptors (NMDARs) and form synapses with glutamatergic neurons throughout the CNS. Although glutamate influences the proliferation and maturation of these progenitors in vitro, the role of NMDAR signaling in oligodendrogenesis and myelination in vivo is not known. Here, we investigated the consequences of genetically deleting the obligatory NMDAR subunit NR1 from OPCs and their oligodendrocyte progeny in the CNS of developing and mature mice. NMDAR-deficient OPCs proliferated normally, achieved appropriate densities in gray and white matter, and differentiated to form major white matter tracts without delay. OPCs also retained their characteristic physiological and morphological properties in the absence of NMDAR signaling and were able to form synapses with glutamatergic axons. However, expression of calcium-permeable AMPA receptors (AMPARs) was enhanced in NMDAR-deficient OPCs. These results suggest that NMDAR signaling is not used to control OPC development but to regulate AMPAR-dependent signaling with surrounding axons, pointing to additional functions for these ubiquitous glial cells.
authors: The Solomon H. Snyder Department of Neuroscience and Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors: Lindsay M
authors: LM
authors: De Biase
authors: Shin H
authors: SH
authors: Kang
authors: Emily G
authors: EG
authors: Baxi
authors: Masahiro
authors: M
authors: Fukaya
authors: Michele L
authors: ML
authors: Pucak
authors: Masayoshi
authors: M
authors: Mishina
authors: Peter A
authors: PA
authors: Calabresi
authors: Dwight E
authors: DE
authors: Bergles
mesh_terms: D000367:Age Factors; D000080924:Aldehyde Dehydrogenase 1 Family; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001703:Biophysics; D001921:Brain / Q000166:cytology* / Q000254:growth & development; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000502:physiology
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008164:Luminescent Proteins; D004676:Myelin Basic Protein; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017461:Receptors, Atrial Natriuretic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D050697:Retinal Dehydrogenase; C409466:NR1 NMDA receptor; C494786:Olig1 protein, mouse; C428743:Rb1cc1 protein, mouse; C515028:ALDH1A1 protein, mouse; C073616:atrial natriuretic factor receptor C