A new mechanism of nervous system plasticity: activity-dependent myelination

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The synapse is the focus of experimental research and theory on the cellular mechanisms of nervous system plasticity and learning, but recent research is expanding the consideration of plasticity into new mechanisms beyond the synapse, notably including the possibility that conduction velocity could be modifiable through changes in myelin to optimize the timing of information transmission through neural circuits. This concept emerges from a confluence of brain imaging that reveals changes in white matter in the human brain during learning, together with cellular studies showing that the process of myelination can be influenced by action potential firing in axons. This Opinion article summarizes the new research on activity-dependent myelination, explores the possible implications of these studies and outlines the potential for new research.

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Figure 1: Development of oligodendrocytes.
Figure 2: Myelin and the node of Ranvier.
Figure 3: Changes in white matter tracts after learning.
Figure 4: Non-synaptic junctions on myelinating glia promote preferential myelination of electrically active axons.
Figure 5: Myelin stabilization is promoted by vesicle release from axons in zebrafish.
Figure 6: Activity-dependent myelination in nervous system plasticity and learning.


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This work was supported by funds for intramural research from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Electron micrographs in Figure 2 are courtesy of Louis Dye, Microscopy Imaging Core, NICHD. 3D reconstruction is courtesy of Emily Benson and Grahame Kidd, Renovo, Inc.

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Correspondence to R. Douglas Fields.

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PowerPoint slides



The cell membrane of an axon.

Fractional anisotropy

(FA). A measure of the symmetry of water diffusion in tissue analysed by MRI. Increased FA reflects more restricted diffusion of water, as occurs when axons become myelinated or more highly compacted, thus restricting water diffusion parallel to the axons.

Non-synaptic transmission

Intercellular communication in the nervous system that does not involve synapses. This includes neurotransmitters released from vesicles fusing with the neuronal membrane outside synapses, as well as the release of neurotransmitters through membrane channels and other mechanisms.

Synaptic coupling

A specialized junction between cells in the nervous system for rapid communication by electrical signalling. Neurotransmitters released from synaptic vesicles in the presynaptic neuron in response to electrical depolarization activate neurotransmitter receptors on the membrane of the postsynaptic cell to depolarize or hyperpolarize the postsynaptic membrane potential.

Uncinate fasciculus

A white matter tract that connects the hippocampus, amygdala and temporal lobe with the orbitofrontal cortex of the brain.

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Fields, R. A new mechanism of nervous system plasticity: activity-dependent myelination. Nat Rev Neurosci 16, 756–767 (2015) doi:10.1038/nrn4023

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