期刊
NATURE NEUROSCIENCE
卷 19, 期 9, 页码 1210-1217出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4351
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资金
- European Research Council [293544]
- Wellcome Trust [100269/Z/12/Z]
- Biotechnology and Biological Sciences Research Council [BB/L003236/1]
- National Natural Science Foundation of China [31471013]
- BBSRC [BB/L003236/1] Funding Source: UKRI
- MRC [G0800575] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L003236/1] Funding Source: researchfish
- Medical Research Council [G0800575] Funding Source: researchfish
- Wellcome Trust [100269/Z/12/Z] Funding Source: researchfish
- European Research Council (ERC) [293544] Funding Source: European Research Council (ERC)
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 similar to 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.
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