Myelination and the Active Brain
When you practice a new cognitive skill, like learning a language, or perform a new motor skill, like learning to swim, you activate pathways in your brain in new ways. We have long known that, when you learn or practice new skills, your brain creates new connections between neurons (called synapses) or modifies existing connections. Several recent studies implicate certain brain cells called oligodendrocytes, and the myelin sheaths they create around our neurons, as also playing an important role in learning or performance enhancement.
Much of the myelination of our brain occurs during early development. During this period, immature cells called oligodendrocyte progenitor cells (OPCs) grow into mature oligodendrocytes, which then produce the myelin sheaths that envelop neurons. A sizeable population of OPCs exists in the adult brain as well, and they can mature into oligodendrocytes after brain injury or demyelination. Indeed, remyelination may occur in the early stages of MS, but in later stages this remyelination fails.
The brain is made up of white and grey matter. Grey matter includes the cell bodies, dendrites, axon terminals of neurons, and the synapses between neurons, while white matter contains the neuronal axon, and the myelin sheaths surrounding them. connections between neurons—are important for learning and brain plasticity. Current research suggests that new myelination, mediated by oligodedrocytes, also plays an important role in learning and adaptation.
Other than helping to recover from injury or disease, is there another role for these OPCs in the adult brain? The answer appears to be “yes”—the OPCs that develop into oligodendrocytes to create myelin may play a role in learning or performance improvement. Additional myelin observed in certain parts of the brain has been associated with various pursuits, such as learning to play the piano. The brain includes both grey matter (which contains the neuronal cell bodies) and white matter (which contains the myelinated portion of the neuron, and oligodendrocytes). Previous studies have shown changes in the grey matter during learning, but more recent MRI studies tracked changes in the white matter of people practicing complex tasks.
When we practice and learn complex tasks, what changes are occurring on the cellular level in these “white matter” regions of our brain? To answer this, two recent studies focused on the role of this “white matter” in motor skill learning, or performance enhancement in mice.
In a recent study, McKenzie and colleagues genetically engineered a strain of mice that could be treated to inactivate the myelination process by blocking the production of new oligodendrocytes. In these mice, the scientists could decrease the number of new oligodendrocytes formed in the brain, without affecting existing oligodendrocytes. The scientists then tested the ability of both the normal and genetically engineered mice to learn a complex new task—running on wheels with unevenly-placed missing rungs. In normal mice, this task increased the number of new oligodendrocytes in their brains, relative to mice who have never experienced wheel running before, and to mice without a wheel. Mice that had a limited ability to produce new oligodendrocytes could not adapt as well to this complex wheel task, and could not run as fast. Hence, it appears that myelin creation by new oligodendrocytes is important in learning a new motor skill.
Another study looked more closely at the changes going on at the cellular level in the mouse brain in response to performance enhancement. Erin Gibson and colleagues bred mice in which certain neurons could be stimulated by shining blue light on them, using small optical fibers implanted in the brain. Stimulation of a specific region of the mice’s brain caused them to move parts of the body that the brain region controlled. Activation of these neurons by the light resulted in an increase in new cells, including a significant number of OPCs, in the brain regions that were activated. Furthermore, this neuronal stimulation appeared to influence oligodendrocyte maturation, and myelin sheath thickness. These cellular changes were also associated with enhanced motor function. Most striking, when the formation of oligodendrocytes was blocked in these mice, there was no effect of the light stimulation on myelination and no enhancement of motor function. Therefore, it seems that new oligodendrocyte formation mediates the effects of activated neurons on myelination and enhanced motor performance.
These scientists examined how new myelin producing cells, or new myelin, might be instrumental in learning and adaptation. But how might the neural activity that leads to learning or adaptation increase myelination? Uncovering how myelination is regulated by activated neurons is an important piece of this puzzle. What secreted molecules might the neurons—activated by learning or other stimulation—be sending to the oligodendrocytes to cause them to produce myelin? Could we use these molecules to stimulate myelination, or the generation of more oligodendrocytes, in other situations? Understanding how to encourage the myelination of neurons could potentially help us design new treatments for remyelination of neuronal circuits affected by multiple sclerosis.
Jan Scholz, Miriam C Klein, Timothy E J Behrens, and Heidi Johansen-Berg. Training induces changes in white-matter architecture. Nature Neuroscience 12, 1370 – 1371 (2009)
Ian A. McKenzie, David Ohayon, Huiliang Li, Joana Paes de Faria, Ben Emery, Koujiro Tohyama, William D. Richardson. Motor skill learning requires active central myelination. Science 17 October 2014: Vol. 346 no. 6207 pp. 318-322
Erin M. Gibson, David Purger, Christopher W. Mount, Andrea K. Goldstein, Grant L. Lin, Lauren S. Wood,Ingrid Inema, Sarah E. Miller, Gregor Bieri, J. Bradley Zuchero, Ben A. Barres, Pamelyn J. Woo, Hannes Vogel, Michelle Monje. Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain. Science 2 May 2014: Vol. 344 no. 6183
T. Burrell. Brain boosting: It’s not just grey matter that matters. NewScientist. 2015.Feb 21: 30-33