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Motor skill learning requires active central myelination
Open accessAbstract
Myelin-forming oligodendrocytes (OLs) are formed continuously in the healthy adult brain. In this work, we study the function of these late-forming cells and the myelin they produce. Learning a new motor skill (such as juggling) alters the structure of the brain’s white matter, which contains many OLs, suggesting that late-born OLs might contribute to motor learning. Consistent with this idea, we show that production of newly formed OLs is briefly accelerated in mice that learn a new skill (running on a “complex wheel” with irregularly spaced rungs). By genetically manipulating the transcription factor myelin regulatory factor in OL precursors, we blocked production of new OLs during adulthood without affecting preexisting OLs or myelin. This prevented the mice from mastering the complex wheel. Thus, generation of new OLs and myelin is important for learning motor skills.
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“In the mouse, motor learning or motor behavioral improvements require proliferation and differentiation of oligodendrocyte precursor cells (OPCs) in the white matter and motor cortex (Gibson et al., 2014 ; McKenzie et al., 2014 ; Xiao et al., 2016 ).”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as McKenzie et al., 2014
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“We focused on the primary motor cortex (M1), as the proliferation and differentiation of M1 OPCs is accelerated, and the activity of M1 cortical neurons dynamically changes during motor learning (Huber et al., 2012 ; Masamizu et al., 2014 ; McKenzie et al., 2014 ; Peters, Chen, & Komiyama, 2014 ; Xiao et al., 2016 ).”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as McKenzie et al., 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“In such a case, the synchronous input of myelinated long‐range axons connecting distant areas, and information processes with a high signal‐to‐noise ratio, may be important (Gibson et al., 2014 ; McKenzie et al., 2014 ; Xiao et al., 2016 ).”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as McKenzie et al., 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“These assessed motor learning ability using a running wheel with irregularly spaced rungs, in which the mice had to coordinate many parts of the body to avoid missing their step, even in the first session.”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as McKenzie et al., 2014
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“running on the wheel leads to an increase in the number of proliferating OPCs after 4 days, followed by an increase in oligodendrocytes after 8 days (20).”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [20]
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“increased motor skills were already apparent after 2 days in wild type mice, but not in mutant mice that were unable to synthesize new myelin (20)”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [20]
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“the density of BCAS1+ oligodendrocytes in the cortex remains high throughout life—in stark contrast to the white matter—supporting a physiological role in neuronal function, e.g. as effectors of adaptive cortical myelination and circuit modulation.49,50”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [50]
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“It is now known that task learning can alter dMRI attributes (Hofstetter et al., 2013; McKenzie et al., 2014; Sampaio-Baptista et al., 2013; Xiao et al., 2016)”
From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as McKenzie et al., 2014
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“Recent evidence in animal models indicates that ongoing myelin remodeling throughout life may be important for learning, behavior, and cognition throughout adulthood (Liu et al., 2012; McKenzie et al., 2014).”
From Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination (2016) · cites this paper as McKenzie et al., 2014
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“Genetic deletion of myelin regulatory factor causes deficient maturation of OPCs in mature mice, resulting in impaired motor learning (McKenzie et al., 2014 ; Xiao et al., 2016 ).”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as McKenzie et al., 2014
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“In contrast to our results, the effect of impaired myelin regulation was detected from the beginning of motor training in other studies (McKenzie et al., 2014 ; Xiao et al., 2016 ).”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as McKenzie et al., 2014
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“a process that requires active myelination (20).”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [20]
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“suggesting that oligodendrocyte lineage cells contribute to learning already within the first 2 days.”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [20]
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“Indeed, the growing realisation that experience can alter white matter microstructure (Metzler-Baddeley et al., 2017; (McKenzie et al., 2014) Zatorre et al., 2012) highlights the problems of separating cause from effect.”
From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as McKenzie et al., 2014
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Metadata
- Authors
- McKenzie, I. A., Ohayon, D., Li, H., Paes de Faria, J., Emery, B., Tohyama, K., & Richardson, W. D.
- Affiliations
- University College London (GB)
- The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
- The University of Melbourne (AU)
- Iwate Medical University (JP)
- Corresponding author
- McKenzie, Ian A.
- Ohayon, David
- Richardson, William D.
- Venue
- Science
- Published
- 2014-10-17
- Volume
- 346
- Issue
- 6207
- Pages
- 318-322
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6324726
- OpenAlex
- W2085529478
- Cited by
- 1,177
- References
- 36
- Citations by year
- 2026: 68 · 2025: 90 · 2024: 103 · 2023: 107 · 2022: 101 · 2021: 146 · 2020: 108 · 2019: 122 · 2018: 83 · 2017: 101 · 2016: 88 · 2015: 53 · 2014: 3
- FWCI
- 28.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (100269, 100269/Z/12/Z, 066745)
- Biotechnology and Biological Sciences Research Council (BB/L003236/1)
- Japan Society for the Promotion of Science (24650181)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- motor skill learning, oligodendrocyte myelination, adult neurogenesis, white matter plasticity, oligodendrocyte precursor cells, juggling
- MeSH terms
- Animals, Brain, Humans, Learning, Male, Mice, Transgenic, Motor Skills, Myelin Sheath, Synaptic Transmission, Oligodendroglia, Mental Recall, Transcription Factors, Gene Deletion, Cell Proliferation, Mice
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