Active brain regions make more myelin
Australian research probes the link between white matter and activity. Fiona McMillan reports.
New research shows that increased electrical activity in an individual neuron leads to a thicker myelin coating around its axon, which can help speed up the transmission of neural signals.
The brain’s grey matter is primarily made up of the main cell bodies of neurons, whereas the white matter largely consists of the long, fibrous axons that carry electrical signals between them.
These axons are coated with a fatty layer of myelin that insulates the nerve fibres and facilitates conductivity. The more myelin, the faster the signal.
Myelin is produced when oligodendrocyte progenitor cells (OPCs) in the central nervous system detect a “need more myelin” signal and mature into the oligodendrocytes that actually make it.
It’s also known that learning new skills such as juggling or playing piano can induce long-term changes in the structure of white matter in humans. Moreover, mice that are unable to make new myelin have trouble learning complex motor tasks.
Toby Merson of the Australian Regenerative Medicine Institute at Monash University in Melbourne, Australia, explains that through these and other studies “we’ve come to understand that electrical activity within axons in the central nervous system is able to stimulate more myelin to be produced”.
However, it was unknown if it is a general process where more activity in a brain area leads to more myelin, or whether it is a precise mechanism where the myelin is targeted to the active axons.
To find out, Merson and his colleagues increased the activity of a subset of neurons in the brains of mice, then checked to see if myelination also increased in these particular neurons.
First, they genetically modified the mice so that a small number of neurons expressed a receptor that triggers neuron activity only in the presence of a drug called clozapine-N-oxide (CNO).
The researchers were then able to stimulate neuron activity very specifically by administering CNO.
“When we looked at the [active] axons we found they were more myelinated,” says Merson. “The adjacent axons that we hadn’t modified were unchanged.”
To determine how myelin-making cells responded when the neurons became more active, the researchers tagged OPCs with a gene for a fluorescent protein, so that they glowed as they matured into active oligodendrocytes.
Visual analysis confirmed these cells were not responding randomly.
“They were preferentially myelinating the axons that we had activated,” explains Merson.
It appears there is a precise mechanism enabling myelin to be recruited to the axons that need it most.
“In development or in plasticity of the brain, you would want those axons to be functioning more efficiently and firing faster, and myelination is the mechanism through which that can be achieved,” says Merson.
Now that he knows how finely tuned the myelination response can be, he is investigating whether the electrical activity of the axon brings this about through direct interaction with nearby OPCs.
It’s not only an important fundamental biological question, he says, but could also reveal new therapeutic avenues for demyelinating diseases like multiple sclerosis.