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Myelin plasticity: sculpting circuits in learning and memory

Abstract

Throughout our lifespan, new sensory experiences and learning continually shape our neuronal circuits to form new memories. Plasticity at the level of synapses has been recognized and studied for decades, but recent work has revealed an additional form of plasticity — affecting oligodendrocytes and the myelin sheaths they produce — that plays a crucial role in learning and memory. In this Review, we summarize recent work characterizing plasticity in the oligodendrocyte lineage following sensory experience and learning, the physiological and behavioural consequences of manipulating that plasticity, and the evidence for oligodendrocyte and myelin dysfunction in neurodevelopmental disorders with cognitive symptoms. We also discuss the limitations of existing approaches and the conceptual and technical advances that are needed to move forward this rapidly developing field.

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Fig. 1: Forms of plasticity within the oligodendrocyte lineage.
Fig. 2: Modulation of neuronal function and plasticity by oligodendroglia and myelin.

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Acknowledgements

We are grateful to M. Kheirbek, R. Roth and members of the Chan lab for their valuable input on the manuscript. We apologize for the omission of many important studies due to space constraints. This work was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (grants R01NS097428 & R01NS095889 to JRC and grant F32NS116214 to WX), the Adelson Medical Research Foundation (ANDP grant A130141 to JRC), and the Rachleff family endowment.

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W.X. researched the data for the article and wrote the article. Both authors made substantial contributions to the discussion of content and reviewed and edited the article before submission.

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Correspondence to Wendy Xin or Jonah R. Chan.

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Nature Reviews Neuroscience thanks G. Corfas, H. Johansen-Berg (who co-reviewed with M. Kaller), W. Richardson (who co-reviewed with M. Swire) and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Genetic fate mapping

A technique that uses genetic methods, such as Cre recombinase, to selectively express a reporter gene in a subset of cells and follow their developmental fate over time.

Barrel cortex

Whisker-related primary somatosensory cortex.

Enriched environment

An environment designed to provide enhanced multisensory stimulation.

Memory consolidation

A process during which recent learned experiences are stabilized into long-term memory.

Contextual fear conditioning

(CFC). A behavioural paradigm in which a novel context is paired with an aversive stimulus (e.g. a foot shock), thereby inducing a learned association between the previously neutral context and the aversive experience.

Cre driver

A genetically engineered rodent line in which Cre recombinase is expressed under a cell type-specific promoter.

Engrams

Enduring physical changes in a neural circuit that underlie specific memories.

Carbon dating

A technique for inferring the age of organic matter (for example, cells) based on the proportion of carbon-14 it contains relative to other carbon isotopes and historical atmospheric proportions of carbon-14.

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Xin, W., Chan, J.R. Myelin plasticity: sculpting circuits in learning and memory. Nat Rev Neurosci 21, 682–694 (2020). https://doi.org/10.1038/s41583-020-00379-8

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