Glia and the Other Type of Brain Plasticity

Historically, the brain has been thought of more like a machine than a biological organ. In its simplest definition, a machine is a collection of structural elements designed to achieve a particular function. A machine uses some type of input—be that energy or information—to generate an output. This is the case for simple machines like pullies and wheels to more complex machines like combustion engines and computers.

Thinking of the brain as a machine is helpful in generating a basic understanding of how it works. Its structural elements are the neurons. And collectively, the brain uses stimuli from the environment as input to generate different emotional states, behaviours, and physical outputs.

There is one crucial distinction, however, between brain and machine that has left a certain aspect of brain biology underappreciated for decades. Unless acted upon by some outside entity, a machine is unchanging. Left to its own devices, the structural elements of a machine and the interactions between those elements will remain unchanged. A machine will take an input and produce the same output the same way, every time, for all time.

The brain, on the other hand, is living. And because it’s living it adapts. It changes with experience. The structural elements that make up the brain—the neurons—change. Connections between neurons are lost and gained. New neurons are added, old ones lost.

The brain’s ability to adapt is referred to as plasticity. The shift in thinking from the brain as static to dynamic was a revolution. Perceptions of learning and recovery from injury, especially in adulthood and old age, changed as a result. But that was just the beginning.

Early work looked at plasticity strictly in terms of the neuron. Learning a skill or consolidating a memory, for example, increases the connectivity of neurons working together while depressing unused connections.

It is now known that other types of cells in the brain, called glia, also contribute to plasticity.

Glia is an all-encompassing term referring to anything in the brain that is not a neuron. This includes oligodendrocytes, astrocytes, ependymal cells, and microglia. These different cells are found in different places and perform different roles.

Oligodendrocytes and the myelin they produce are key players in this other type of plasticity. In response to activity within a neuron, oligodendrocytes reach out their tentacle-like arms and wrap segments of nerve fibers, altering the speed electrical signals can travel and provide additional nutritional support. This other type of plasticity is called adaptive myelination. I’ve touched on it before in previous posts.

This article is about one of the other types of glia: astrocytes. As researchers have peeled back the layers of the onion that is brain plasticity, they’ve discovered several ways in which astrocytes contribute to adaptive myelination.

Of all the glial cells, astrocytes are the most abundant. They’re scattered all over the brain and spinal cord, perfectly positioning them to modulate function and aid in communication between different cell types.

Astrocytes help oligodendrocytes respond to neural activity

Before an oligodendrocyte becomes an oligodendrocyte that produces myelin, it starts as an oligodendrocyte precursor cell. From there it becomes a premyelinating oligodendrocyte. Then finally a myelinating oligodendrocyte. Astrocytes oversee this three-stage process and can initiate the cascade from precursor to myelinating oligodendrocyte in response to electrical activity in a neuron.

Neurons communicate with one another by sending electrical impulses, called action potentials. These action potentials travel away from the body of the neuron along a long wiry extension called an axon (more commonly known as a nerve fiber).

As the electrical impulse travels along the nerve fiber, a molecule called ATP is released into the surrounding space.

Astrocytes in the vicinity of the nerve fiber respond to the ATP by releasing a protein called LIF.

LIF, in turn, promotes the myelination of nerve fibers by oligodendrocytes.

In this way, frequently used neural circuits can increase the speed information is transferred within it. The more it’s used, the more action potentials will be traveling along the nerve fibers. The more action potentials, the more ATP and the more LIF, which all culminates in increased myelination and increased conduction speed within the circuit.

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Astrocytes provide oligodendrocytes with the building blocks of myelin

Myelin is an extension of the oligodendrocyte membrane and is made up of mostly fat molecules (lipids)—it’s 70-85% lipid, which is contrary to the average cell membrane, which is dominated by protein.

Because myelin is an extension of the oligodendrocyte cell membrane, it means the oligodendrocyte has to manufacturer a huge amount of membrane, which is energetically expensive and requires a lot of building materials. These building materials have to come from somewhere.

Astrocytes supplement oligodendrocytes with lipids for the making of myelin. A group of researchers working out of the Department of Neuroscience at Karolinska Institutet in Sweden showed that deleting a lipid synthesis gene in oligodendrocytes during development did not impede myelination. Deleting the same lipid synthesis gene in astrocytes, however, resulted in less myelin being deposited.

Somehow, astrocytes are able to transfer lipids to oligodendrocytes for myelin synthesis. This has only been described during development, but a similar mechanism may exist for the rapid supply of lipids required during adaptive myelination.

Astrocytes regulate myelin thickness and length

Myelin contributes to the synchronizing of neural networks by regulating the speed action potentials travel, controlling when information arrives at certain places. Myelin regulates speed with the thickness and length of the myelin sheath. To a certain point, the thicker myelin is, the easier it is for electrical impulses to move, and the faster they travel.

Furthermore, the longer the myelin sheath is, the longer an impulse can travel with relative ease. Again, allowing it to move faster along the length of the nerve fiber.

Astrocytes interact with myelin and nerve fibers at gaps in the myelin sheath called the nodes of Ranvier. Here, researchers have shown astrocytes can alter myelin thickness and length through their ability to regulate the destruction of a protein important in securing myelin to the axon at these junctions.

In the study, when astrocytes were inhibited from releasing a factor that prevented the myelin securing protein from being degraded, myelin became thinner and the gap between adjacent myelin sheaths got larger (i.e. there was more bare axon exposed). The consequence of these alterations was decreased conduction velocity.

By allowing the myelin anchoring protein to be degraded, this could be a way astrocytes contribute to myelin thinning in areas of the brain with less neural activity.

Astrocytes control brain blood flow in response to neural activity

Neural activity requires energy as ion balances across the membrane of the nerve fiber must be restored after an action potential goes by. The more neural activity, the more energy required. And the more energy required means more oxygen is needed, which is delivered to working brain regions via the blood.

Astrocytes play an important role as an intermediary between increased neural activity and increased blood flow. In response to neural activity, calcium levels within astrocytes rise, causing them to release factors that trigger the vasodilation (blood vessels get larger allowing more blood flow) of nearby blood vessels.

Increased blood flow to highly active areas of the brain may be one of the triggers of adaptive myelination. When blood flow is increased, the cells lining blood vessels release a protein called endothelin. Endothelin has been observed to increase myelination by oligodendrocytes.