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Inside your head, another brain is hiding in plain sight 鈥� one that responds to your cognitive needs and self-heals. It鈥檚 time to make the most of your myelin

RECENTLY, my friend鈥檚 cable TV went out. She fiddled with the box: resetting, unplugging and re-plugging. When that failed, she called the cable company. They examined things at their end 鈥� and came up short. Frustrated, she retreated to another room, where she discovered her cat had ripped apart a piece of the wire. It wasn鈥檛 the ends that needed fixing; it was the part in the middle.

A similar revelation is under way in neuroscience. For years, changes in the brain 鈥� whether from learning to ride a bike, taking a Prozac, or sinking into Alzheimer鈥檚 disease 鈥� have been attributed to the activity of neurons and the small chemical junctions between them, called synapses. Targeting synapses is like fiddling with the connections at either end or calling the cable company. But ignoring the wiring in between may be a mistake.

鈥淎ll ideas about communication and plasticity in the nervous system were focused on the synapse,鈥� says at the National Institutes of Health in Bethesda, Maryland. That鈥檚 starting to change, as he and other neuroscientists realise that neurons alone are not enough to explain our brain鈥檚 plasticity 鈥� its ability to learn, adapt, and form new memories.

(Image: Sam Falconer)

What it comes down to is myelin, the fatty sheath that envelops most neurons. We are used to thinking of it like insulation along a cable 鈥� allowing electrical impulses to zip along faster. But we are learning that this fatty layer is not like a wire鈥檚 insulation, installed uniformly and left unattended. Instead, it is dynamic and autonomous, customising itself to match the brain鈥檚 demands. The cells that produce it respond in real time to our cognitive needs: new insulation is laid down to help the brain master a skill; a frayed section can be replaced. What鈥檚 more, these additions and renovations continue well into adulthood. This new kind of plasticity has come as a shock to many researchers. at Georgetown University in Washington DC has been a professor of neuroscience for over a decade, but when he heard about it last year, he was gobsmacked. 鈥淲ait, really?鈥� was all he could mutter.

And plasticity is just the start. Because they are not nerve cells, which are notoriously hard to tinker with, we might be able to tweak them manually to give the brain an extra boost when needed, or to help mend the damage behind conditions such as multiple sclerosis. It turns out a most vital part of our cognitive potential has been hiding in plain sight.

To better understand why myelin is so important, you need to look at how information travels around the brain. A neuron sends electrical impulses zipping down long projections called axons to the synapse, a small gap that chemicals called neurotransmitters travel across. These relay the signal to neighbouring neurons (see diagram). Myelin keeps the information tightly confined within the axon, allowing a speedy trip.FIG-mg30090601.jpg

Wired for learning

The substance is thought to have evolved to allow animals to react quickly. But myelin does more than just speed up our reflexes, it is also crucial to learning, development and behaviour. 鈥淯ltimately it allows us to have clever brains,鈥� says , who studies neuronal plasticity at University College London.

Hints about the role of myelination in cognitive abilities come from the way it is produced during our lifetime. A small amount is made as we develop in the womb, but after birth it takes off, and we see surges as infants learn to crawl, walk and talk. By about age 4, the rate of myelination slows, and teenagers still have the prefrontal cortex left to myelinate 鈥� an area crucial for planning and consideration of consequences. Until then, processing in the prefrontal cortex is slow and inefficient and teens remain precariously impulsive. The finer circuitry is complete by the time we reach our 40s, but from the 60s onwards the coverings start to fray and degenerate, which fits with the common experience of cognitive decline as we age. As myelin degenerates, the signals get fuzzier.

Until recently, scientists thought insulating the prefrontal cortex was the final hurrah for myelin. Plasticity was then down to the neurons, and synapses between them. For instance, the number of neurotransmitter receptors increase in a synapse the more that pathway is used, which enables the brain to adapt according to learning or experience. As a result, our quest to understand cognitive decline, and the potential for activities that boost brain power, has focused on grey matter, the part of the brain and spinal cord packed with the neuron cell bodies and synapses.

But at the University of Oxford began to wonder about white matter, the area of our brain that is rich in myelin-covered axons. 鈥淚t seemed like an overlooked but obviously very important structure in the central nervous system,鈥� she says. It wasn鈥檛 until 2009 that she could investigate, with the help of a new neuroimaging method called diffusion MRI, which accurately measures human white matter in the living brain.

To test her idea, Johansen-Berg turned to a 2004 study, which had found that such as juggling changed the density of grey matter 鈥� an example of classic synaptic plasticity. Johansen-Berg decided to recreate the study, and measure changes in white matter too. A group of volunteers agreed to learn how to juggle, and after six weeks, brain scans showed that their myelin had increased more than that of a control group who had no training ().

鈥淲e saw a change not only in the grey matter but also in the underlying white matter pathways, suggesting that these pathways strengthen in some way as a result of experience,鈥� says Johansen-Berg. The changes to white and grey matter took place over different timescales, suggesting two separate processes. Johansen-Berg thinks the increase in white matter would have enabled faster conduction along the circuits coordinating juggling. What鈥檚 more, the effect was seen in everyone who learned to juggle, regardless of how good they became, which means it is the learning process itself that is responsible.

This was the first study to reveal that training can alter white matter in healthy adults, and it opened the door to a plethora of similar findings. Since then, numerous activities have been linked to extra myelin, from , to , and learning a new skill like or .

To investigate these changes more closely, Richardson turned to rodents. Rather than juggle, he made mice run on a complicated wheel, with rungs removed in a random pattern. Watching the struggling mice is a pitiful sight 鈥� their legs slip through the bars, their paws feel desperately into empty space. But after just a few days, they look like they鈥檝e been doing it forever. So was myelin the key?

Myelin is formed by oligodendrocytes, octopus-shaped cells with long arms that wrap thin layers of fat 50 to 100 times around the axon, preventing electrical signals from slipping out, and expediting the conversation between brain regions (see diagram). by oligodendrocyte precursor cells (OPCs), which tile the brain, ready to morph when needed.FIG-mg30090601.jpg

When Richardson bred mice that couldn鈥檛 produce oligodendrocytes 鈥� or new myelin 鈥� in adulthood, the mice weren鈥檛 able to get used to the wheel, even after a week of practice.

Further proof of the essential role of myelin in learning complex skills came last year. Michelle Monje at Stanford University in California turned to another relatively new technology, optogenetics, which involves breeding mice with light-sensitive genes. This allows unprecedented control over neurons using pulses of light. Monje used it to activate a particular set of neurons that made the mice run in anticlockwise circles. After a while, they became slightly more efficient with the left paw, and when Monje inspected the brains of the mice, she found that new myelin had been laid down in these circuits. Crucially, she was able to show that repeatedly activating specific neurons led to changes in the surrounding myelin , so it was this that was critical to making the circuits more efficient.

Richardson and Monje鈥檚 papers, both published in 2014, distinguish myelin plasticity as a second type of plasticity 鈥� distinct from the better-known synaptic version. Although more studies will be needed in humans, the findings have important implications for learning and memory. Well-used pathways get more myelin, as shown in the juggling study, speeding up the signals and making the brain more efficient. Being more efficient, these pathways are also more likely to be used next time around. 鈥淚t鈥檚 not only that information is stored in the plasticity of synapses, but actually in the myelin as well,鈥� says at the University of Michigan in Ann Arbor. If you are learning Mandarin, for instance, myelination would help you remember the right character faster and more intuitively. 鈥淭his gives a new dimension to the amount of information and the types of information the nervous system can store,鈥� Corfas says. The importance of these and other non-neuronal cells has led Fields to term them our 鈥渙ther brain鈥�.

While we now know that stimulating the brain in various ways can boost myelin production, so too can the insulation be lost, emphasising that the brain is a 鈥渦se it or lose it鈥� organ. If electricity isn鈥檛 flowing, the myelin can degrade, and this can lead to psychological and social problems (see 鈥�Social networks鈥�). If the brain were a city, and myelin the insulation on wires connecting the buildings, some parts would end up in the dark. A lack of myelin is implicated in conditions like autism, in mental illnesses such as schizophrenia, and in spinal cord and traumatic brain injuries.

And there is a further twist. It turns out that myelin production is in part controlled by packets of messenger chemicals that are relayed through the blood. Could we use these messengers to give struggling brains a boost, rather than trying to manipulate brain cells directly, which is notoriously hard?

That鈥檚 the thinking behind the work of , at the University of Chicago. His team discovered that small packets of proteins and RNA in the blood known as exosomes influence myelin production.

Many types of cell release exosomes as a way of delivering specific messages to other cells: they are part of the body鈥檚 vast communication network. Kraig began to wonder about the roles of exosomes on brain function after reading that transferring the blood of young mice into old mice can reverse their cognitive decline.

He has now shown that exosomes produced in the blood are taken up by OPCs in the brain. Their message is the 鈥渢rigger to make the myelination go鈥�, says Kraig. That raises the exciting possibility that a blood transfusion packed with the right exosomes could help treat multiple sclerosis (MS), in which myelin is attacked by the immune system.

OPC-regulating exosomes are dispensed whenever the brain is stimulated in new ways, such as during exercise and learning. They may be one reason why physical and mental activity help ward off diseases like Alzheimer鈥檚. But while advice to exercise the body and mind is not new, for many people it is not that simple 鈥� if you have MS, for instance. Kraig hopes that treating people with lab-made exosomes that can be delivered nasally might improve myelination enough to enable them to exercise, and thus boost exosomes and myelination themselves.

Another disease, amyotrophic lateral sclerosis (ALS), is not normally associated with myelin. It is characterised by the death of neurons that control muscles. But in 2013, at Johns Hopkins University in Baltimore, Maryland, showed in mice that oligodendrocytes die before the neurons. Late in the disease, more than half of them had died. 鈥淭his is a massive reorganisation of myelin. It is very stressful for neurons and can induce them to degenerate,鈥� Bergles says.

He has now found that in people with ALS, OPCs seem to have difficulty converting to oligodendrocytes. The key to an ALS cure may lie in preventing the initial oligodendrocyte loss, or helping OPCs to morph properly.

There is still much to be worked out, and many of the animal studies need to be confirmed in humans. But as Corfas said at the Society for Neuroscience conference in Washington DC last November, 鈥渋t鈥檚 an exciting time. The way we think about myelin is changing.鈥� Indeed, if we can uncover enough, this type of research might even yield an actual wonder drug, says Richardson, one that makes us smarter, speeding up the rate of learning.

鈥淭his research might yield a wonder drug that speeds up the rate of learning鈥�

In the meantime, the message is clear. 鈥淜eep learning, keep your mind active,鈥� Richardson says. Kraig recommends learning new things, like a new piano piece, as well as keeping up with ordinary activities like taking a walk. If it鈥檚 an unfamiliar route, with changing scenery and the requirement to memorise the way home, that鈥檚 all to the good. So embrace a new hobby. And then another. It should help keep the electricity flowing a little better, a little longer.

This article appeared in print under the headline 鈥淢eet your other brain鈥�