title: Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes.
abstract: Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. In vivo, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Iben
authors.initials: I
authors.lastname: Lundgaard
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Aryna
authors.initials: A
authors.lastname: Luzhynskaya
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: John H
authors.initials: JH
authors.lastname: Stockley
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Evans
authors.affiliation: MRC Centre for Regenerative Medicine, Centre for Multiple Sclerosis Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Swire
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Katrin
authors.initials: K
authors.lastname: Volbracht
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Hélène O B
authors.initials: HO
authors.lastname: Gautier
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.affiliation: MRC Centre for Regenerative Medicine, Centre for Multiple Sclerosis Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Attwell
authors.affiliation: Wellcome Trust-Medical Research Council (MRC) Stem Cell Institute, John van Geest Centre for Brain Repair, and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ragnhildur T
authors.initials: RT
authors.lastname: Káradóttir
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods; D005260:Female; D009186:Myelin Sheath / Q000502:physiology*; D020890:Neuregulin-1 / Q000502:physiology; D020880:Neuregulins / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020890:Neuregulin-1; D020880:Neuregulins; C490580:Nrg1 protein, rat; D016194:Receptors, N-Methyl-D-Aspartate