title: Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning.
abstract: We identified mRNA encoding the ecto-enzyme Enpp6 as a marker of newly forming oligodendrocytes, and used Enpp6 in situ hybridization to track oligodendrocyte differentiation in adult mice as they learned a motor skill (running on a wheel with unevenly spaced rungs). Within just 2.5 h of exposure to the complex wheel, production of Enpp6-expressing immature oligodendrocytes was accelerated in subcortical white matter; within 4 h, it was accelerated in motor cortex. Conditional deletion of myelin regulatory factor (Myrf) in oligodendrocyte precursors blocked formation of new Enpp6(+) oligodendrocytes and impaired learning within the same ∼2-3 h time frame. This very early requirement for oligodendrocytes suggests a direct and active role in learning, closely linked to synaptic strengthening. Running performance of normal mice continued to improve over the following week accompanied by secondary waves of oligodendrocyte precursor proliferation and differentiation. We concluded that new oligodendrocytes contribute to both early and late stages of motor skill learning.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.|Institute of Neuroscience, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: David
authors.initials: D
authors.lastname: Ohayon
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: Ian A
authors.initials: IA
authors.lastname: McKenzie
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sinclair-Wilson
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Fudge
authors.affiliation: Jungers Center for Neurosciences Research, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098.
authors.forename: Ben
authors.initials: B
authors.lastname: Emery
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: Huiliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT.
authors.forename: William D
authors.initials: WD
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008822:Mice, Transgenic; D009048:Motor Skills / Q000502:physiology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D013997:Time Factors
chemical_list: D004676:Myelin Basic Protein