Previously, on Know Your Neurons:
Chapter 1: The Discovery and Naming of the Neuron
Chapter 2: How to Classify Different Types of Neurons, or The Dendrology of the Neuron Forest
Chapter 3: Know Your Neurons: Meet the Glia
*By Daisy Yuhas
Trillions of cells in your brain communicate with one another, respond to infections, guide tissue development and support learning and memory—but none of these cells are neurons. These cells are known as glia and they outnumber neurons by as much as 50 to one (Edited to Add: More recent evidence suggests that the human brain's glia to neuron ratio is much closer to 1:1. For a thorough discussion, see Chapter 4).
For most of history glia were simply, you know, the 85 percent of brain cells "leftover" when you looked for neurons. Researchers initially assumed that glial cells were just structural filler. Later, hints emerged that glia served as the neurons' helpmate: housekeeper, insulator, occasional nurse. Today, scientists are starting to accept that the brain's other half boasts a repertoire of functions every bit as vital as those of neurons.
Glia's story begins in 1856 with Rudolf Virchow, a German biologist famed for his work in pathology and his dogged dismissal of Darwinism. While hunting for connective tissue in the brain, he identified "a sort of putty" studded with nerve cells. He christened this material nervenkitt in German, or neuroglia from the Greek for "nerve glue." Ten years later, German anatomist Otto Karl Deiters identified some unusual cells amidst this sticky stuff. Because these cells lacked axons—the long slender cables that carry signals away from a neuron's cell body—he surmised that these tailless cells were not neurons. As the century turned, researchers proposed different theories to explain these odd cells and their possible functions. Camillo Golgi used Dieters's criteria to define glial cells, which he believed fed neurons. Santiago Ramón y Cajal posited that glia might be insulators for the electrical activity of neurons. What all descriptions of glial function had in common was the conviction that glia served as passive counterparts to the neurons' active, central role in the brain.
It's hard to fault this perspective. Staining techniques and early microscopes offered only a partial view into glia's tiny world. Besides, neurons display all kinds of exciting electrical activity and glia do not. For a little insight into the perspective of these neuroscientists, imagine you're at a crowded party. As you move through the room, your eyes are invariably drawn to the boisterous, talkative, and vibrant characters who seem to soak up the attention of everyone around them. In fact—and this is a little weird—with the exception of these characters, who only make up a scant 15 percent of the crowd, no one else at the party is talking. This is how neuroscientists understood brain cells for about a century: a few dazzling neurons, and then…glia, the silent, dull majority.
By the early 20th century, however, scientists began to suspect that glia might be up to something. When they counted starry-shaped glial cells called astrocytes in various brains they noticed some peculiar patterns. For example, as Hungarian psychopathologist Ladislas von Meduna noted in the 1930s, individuals suffering from schizophrenia or severe depression had very few astrocytes in the cortex—the outer layer of the brain—while individuals who had experienced an epileptic seizure had an unusually high numbers (the observation inspired the development of electroconvulsive therapy). Fifty years later, neuroscientist Marian Diamond at the University of California Berkeley observed that although Albert Einstein's neuron count and brain size seemed fairly average, his astrocyte count was well above average.
The strangest hint of all emerged in 1966, when Steven Kuffler and colleagues at Harvard exposed glial cells to charged potassium, one of the ions commonly released by neurons after firing. To their surprise, even though glial cells don't have axons—which means they can't carry and send an electric signal—exposure to charged ions still changed the glial cell's charge, a shift very like the first step when a neuron fires. Here was definitive evidence that glial cells could 'respond' to a neuron's signal.
The end of the twentieth century brought the biggest surprise. In a series of experiments conducted throughout the 1980s and 1990s, it became clear that instead of passive witnesses to neuronal activity, glia were actively involved in sending and receiving signals to neurons and other glia. When scientists exposed glial cell cultures to molecular messengers called neurotransmitters, the cells responded by taking in calcium. In 1990, Ann Cornell-Bell and Steven Finkbeiner at Yale documented how the influx of calcium in one glial cell led to a similar influx in neighboring glial cells, creating a wave of calcium uptake that spread across glia. Four years later, Maiken Nedergaard at New York Medical College observed that the calcium wave affected nearby neurons as well as glial cells. Not only do glia respond to a neuron's chemical signals, they also produce their own chemical messages that influence the activity of neurons. In short, glia had been talking—to each other and to neurons—all along, but instead of communicating both electrically and chemically like neurons, they only communicated chemically.
It's not idle chatter, either. "We now realize that glia are involved in every aspect of neuron function," says neurobiologist R. Douglas Fields of the National Institutes of Health. "Glial cells are even more complicated than neurons and involved in many, many more processes." Glial cells maintain the brain's environment, regulate synapses and neurotransmitters, respond to injuries, and in certain cases can even become neurons.
Here's an introductory teaser to five types of glia researchers have discovered so far:
Astrocytes: The star-shaped astrocyte uses thousands of arms to take up neurotransmitters, cleaning up after neuronal activity. Scientists suspect that they're the most common type of glial cell in the brain, and some believe that the calcium waves astrocytes generate may underlie creative thought.
Oligodendrocytes: The octopus-like oligodendrocyte wraps the tips of its tentacles around axons in a fatty white coating called myelin. Studying such 'white matter' may provide insights into intelligence and learning and problems with myelin are at the heart of diseases such as multiple sclerosis.
Schwann cells: Much like an oligodendrocyte's protective tentacles, Schwann cells form a snug layer of myelin around the axon like the bread around a corn dog. As the only glial cell in the peripheral nervous system—the nerves outside the brain and spinal cord—Schwann cells adopt a range of different roles, including astrocyte-like chemical clean ups.
Microglia: While the previous three cells belong to a category called macroglia, there are also smaller microglia. These wee cells are the brain's rapid response team. Since the immune system's molecular machines can't cross the blood-brain barrier, the versatile microglia defend the brain from invaders.
NG2 Cells: Their name may not be that memorable, but NG2s—or the cell previously known as "oligodendrocyte precursor cells"—are big news in the world of glia research and may even constitute a whole new category of macroglia. These cells transform not only into different kinds of glia, such as oligodendrocytes and astrocytes, but also into neurons, further blurring the lines that distinguish the two types of cells.
*Daisy Yuhas is a science writer based in New York and an intern with Scientific American MIND
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