Microglia: A Standing Ovation, Please!

Neurons! Neurons! Neurons! Everyone who thinks and writes about the brain is always shouting BRAVO! for neurons. If you weren't careful, you'd soon conclude that most of that three pounds of mush that you carry inside your skull is worthless. It is only the neurons that count.

I'd like to correct that misconception. Personally, my neurons are big fans of glial cells--yours and mine. In the drama I call Brain Sense, the leading actors, the sensory neurons, often get all the applause, but it's the humble glial cells that are, in fact, delivering a star performance.

First, let's set the record straight. Most of the brain's cells are not neurons. They are glial cells. Somewhere between 1 and 5 trillion glial cells protect and support the neurons of the two hemispheres. The different types of glial cells include

• oligodendrocytes, which form protective sheaths around the axons of neurons
• satellite cells, which surround the cell bodies of neurons
• and neuroglia, which guide the path of growing neurons during fetal development.

Also important are the astrocyctes, or astroglia. Scientists once believed that astroglia merely provide nutrients, support, and insulation for neurons, but recent research suggests they do much more. They "instruct" new, unspecialized brain cells, "teaching" them what kind of mature neuron to become. They also help regulate the transmission of nerve impulses and the formation of connections between brain cells.

Another  type of glial cell is the microglia--long recognized as important cells of the immune system. These cells extend microscopic "arms" into surrounding brain tissue where they clean out dead cells and check for damage. They spring into action--manufacturing disease-fighting chemicals--when the brain is injured or infected.

Now, new research from the University of Rochester Medical Center is revealing even more reasons to stand up and applaud the microglia. It turns out that microglia serve more than immune functions. They are essential to learning and memory.

How? Learning and memory are--in the simplest cellular terms--strong associations within a network of neurons. Neurons do not touch, so they do not wire themselves up like circuits. Instead, chemicals called neurotransmitters carry an impulse across the space (called the synaptic gap or synaptic cleft) between neurons. The more frequently neurons communicate in this way, the stronger the connection becomes. That's what we call learning and memory. When the connection goes unused, we forget. The connection across the synaptic gap grows weaker, perhaps even disappears.

The new research suggests that a lot of what is going on in that synaptic gap is engineered by the microglia. The Rochester research team made this discovery by changing the lighting in the cages of mice. First, the mice lived in a normal cycle of light and dark; then they lived in the dark for several days before a normal light/dark cycle was restored.

The researchers used two imaging techniques to study the microglia in the animals' brains during these various stages. When the lights were off, microglia contacted more synapses, were more likely to reach toward a particular type of synapse, tended to be larger, and were more likely to destroy a synapse. When the lights came back on, most of those activities reversed.

The finding that activity among microglia changed in response to visual inputs was, in itself, surprising. "Just the fact that microglia can sense that something has changed in the environment is a novel idea," says research team leader Ania K. Majewska.

The images revealed that microglia send out their arms constantly, often targeting synapses. The extensions move quickly through the dense circuitry of the brain, traveling perhaps two millionths of a meter in a minute. That is remarkably swift on a molecular scale!

Microglia touch and wrap around synaptic regions constantly, perhaps determining which connections will survive and which will disappear. The team even found indications that microglia may destroy connections through a process known as phagocytosis (which means, literally, "eating cells") of the dendritic spines on neurons. Dendritic spines are essential to neuronal connections. Eliminating them is one way to destroy a connection. In the Rochester study, connections touched by microglia were three times more likely to be eliminated within the next two days compared to spines that were not touched.

Thus, it appears that neurons are going to have to move over and learn to share center stage with the glial cells. Microglia are essential to the brain's ability to adapt immediately and constantly to the environment and to shift its resources accordingly. "The idea that immune cells are always active in our brain, contributing to the ongoing process of learning and memory, really challenges current views of the brain," says the study's first author Marie-Ève Tremblay.

Therefore, I think it's time that we give a standing ovation to microglia and the other glial cells. There would be no performance without them.

For Further Information:

Brain Sense.

Marie-Ève Tremblay, Rebecca L. Lowery, Ania K. Majewska. "Microglial Interactions with Synapses Are Modulated by Visual Experience." PloS Biology, November 2, 2010.

Synapse diagram from ScienceBlogs.com.

Dr. Majewska's lab page.

Department of Neurobiology and Anatomy at the University of Rochester.

Glial cells images from UCLA.

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