There is a guy who gets things done
He lives in the in-between spaces.
He’s the guy who takes care of business. The guy who takes out the trash. The ‘removal man’. The ‘eraser’. The mafia call this guy ‘the cleaner’.
Your brain has one too.
He’s the brain’s hired gun, removing the corpses, executing the soon to be corpses, and disposing of the bodies.
He takes care of the grey matters.
You should meet him.
The grey matter
It’s common to hear the brain referred to as ‘the grey matter’. And, in truth, some of it is.
Most of it isn’t.
The grey matter, formally known as the Substantia grisea, is packed with the cell bodies of neurons, and has a very light grey tinge, given by the density of the cell bodies.
In a cross-section of your brain you can see the grey matter easily, as it’s in contrast to the rest of your brain, seen as white. Simply, white matter refers to the stuff in your brain that isn’t grey. It’s whiter due to having fewer cell bodies, and is made up primarily of myelin, and glia, or glial cells.
Only 15% of your brain’s volume is grey matter. The remainder is the white matter, the myelin and glia.
The white matter
Myelin is the fatty stuff that wraps itself around the long, rope-like axon of neurons, giving them a chain of sausages appearance and helping facilitate the nerve impulse from the cell body down the axon to the end of the cell. In a brain cross-section, you see it particularly in fibres that join one part of the brain to another, either within the cerebrum (the cortex or outer layer of the brain and a few structures underneath it) or between the cerebrum and structures deeper in the brain.
Glial cells, often considered the brain’s glue (glia comes from the Greek meaning glue), are remarkable, and more than simple glue. Myelin is actually an outgrowth of glial cells, and glia also helps maintain structure in the brain by surrounding neurons and holding them in place. The fattiness of glial cells helps insulate neurons, and they provide oxygen and nutrients to brain cells.
But as R. Davidson Fields pointed out in The Other Brain, (no affiliate link) his unfolding of our growing awareness of glia’s abilities, scientists discovered that glia even have their own communication network, in parallel to the more familiar communication system. It’s not electrically governed but manages still to spread information broadly across the brain.
And it’s one of these glial cells, the microglia, that takes care of your messy business, of the clean up.
The cleaner in your brain
Comprising about 15% of glial cells, microglia are roving removal men, efficiently eliminating dead cells, mercilessly executing dying cells and disposing of their bodies. They hunt for the waste byproducts of mental activity such as plaques (deposits of beta-amyloid protein seen in Alzheimer’s disease) and look for infection to deal with. They’re related to white blood cells which perform the same functions outside the brain.
They always seemed to be cannibalistic, living on dead and dying neurons. But more recent work shows they have a broader diet…
A glial diet
At birth, brains have limited white matter, but begin a journey of progressive myelination. Additionally, in the young brain, innumerable new connections are made. Neurons send out fibres from their body, to join with partner neurons nearby, or in different parts of the brain. These connections and pathways are critical for the massive cognitive power the brain harnesses. You’ll remember that the connecting point between two neurons isn’t really a touchpoint, but a microscopic gap-the synapse-where all kinds of mental magic happens.
It’s the synapse across which neurotransmitters flood when released by one cell, to join with receptors on the adjacent cell, activating it or preventing it from activating. It’s in the synapse that psychiatric medications typically work, affecting the quantity and effect of the neurotransmitters there. The more you use a synapse, the stronger the connection between those two cells becomes. It’s an extraordinary place.
But in the developing brain, amidst the morass of new connections, many turn out to be poor quality or wrongly connected, and must be expertly and ruthlessly pruned off. But it’s not a random pruning. This selective cutting literally shapes the developing brain, and is crucial to its connectivity. Removing unnecessary synapses allows room for growth and, like any gardener knows, prune some off and the remaining ones grow stronger.
They must be cleaned up, and microglia feed on the synapses also.
Cornelius Gross, and colleagues, from the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, showed how this happened back in 2011, by demonstrating that proteins found inside the synapse, are found also in the bellies of microglia, evidence of their diet.
Sometimes, they don’t eat enough
Overabundance of connections impairs the ability of connections to grow in strength, as there are simply too many connections to feed, and activity is frenetic and weak rather than deliberate and strong.
Building on his earlier work, Gross and collaborators at the Istituto Italiano di Tecnologia (IIT), in Rovereto, and La Sapienza University in Rome, published new research this week in Nature Neuroscience. They note that for many people with autism (and other neurodevelopmental disorders), different parts of the brain communicate poorly, a result of the microglia failing to prune hard enough because there simply weren’t enough of them.
“We show that a deficit in microglia during development can have widespread and long-lasting effects on brain wiring and behavior,” says Cornelius Gross, “It leads to weak brain connectivity, decreased social behavior, and increased repetitive behavior, all hallmarks of autism.”
Microglia have a significant impact on the developing brain, and directly affect its connectivity and performance. But beyond even their impact in the early years of life, the sheer amount of white matter we have affects us throughout our lifespan.
It changes as we age
We know that in the early years of life the brain proliferates cells and prunes, and then undergoes a similar, slightly smaller-scale process around late childhood/early puberty. White matter, also, changes as we age, and age-related differences in white matter are linked to specific cognitive abilities in childhood and adulthood. And in a study published this week in Biological Psychiatry, Dr. Bart Peters and colleagues of the Zucker Hillside Hospital, investigated age and neurocognitive performance, in relation to nine white matter tracts, from childhood to late adulthood.
“Our study identified key brain circuits that develop during adolescence and young adulthood that are associated with the growth of learning, memory and planning abilities. These findings suggest that young people may not have full capacity of these functions until these connections have completed their normal trajectory of maturation beyond adolescence,” commented Peters.
“Our brain is changing throughout our lives. These changes underlie the capacities that emerge and are refined through adulthood,” explained Dr. John Krystal, Editor of Biological Psychiatry. “There are clues that the steps that we take to preserve our medical health and stimulate our minds also serve to further refine and maintain these connections. For good reasons, attending to brain health is increasingly a focus of healthy aging.”
So here’s the take home bit
Microglia, a subset of your glia, perform the dirty work of removing dead and dying cells. But more than just housekeeping, they are actively responsible for pruning synapses, directly shaping the brain and how it communicates with itself.
Additionally, overall white matter is critical for long-term cognitive performance, and it continues to develop and refine as we age.
Impressive words to drop into the morning coffee chat
Substantia grisea, microglia, glial cells
What do you think?
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