Glia: The Other Brain
Glia--brain function beyond neurons
Posted Dec 15, 2009
With eager hands of a ten-year-old boy I sliced the heart in two with a butcher knife. All was revealed-four chambers separated by moist gristly valves that suck blood into auricles and squeeze it out the aorta and pulmonary artery. Fascinated, I asked Mom, "Next time, can you get me a brain?"
When she returned from the butcher shop with a calf brain my excitement welled as I sliced, cleaving the squishy convoluted mass in two like an over-ripe mellon. But inside there was nothing. Just a hollow cavity at the core of a fleshy mush.
How did it work?
Books offered names for its various bumps and folds-cerebellum, pons, medulla, lateral ventricle-but this information failed to provide the slightest inkling into how this organ-the most supreme of all bodily organs-might function. My parents, teachers, no one, really seemed to have the answers.
Four decades later that scene loops through my mind as vividly as the day I lived it. After years of study and mentorship, and then decades of research in my own lab, the fascination of that day has never diminished. The more I learn about the brain, the more I am fascinated and puzzled by it.
Today I know that the brain's power comes from miniaturizing and concentrating its components to such an extreme that its working parts are invisible. Like the working parts of a computer miniaturized beyond the resolution of the human eye, the working components of the brain are invisible unless they are magnified hundreds or thousands of times larger by powerful microscopes.
A century ago the newly perfected optical instrument gave scientists their first look at the cellular structure of brain tissue. What these pioneering scientists glimpsed through that window into brain tissue astonished them. Brain cells were unlike those anywhere else in the body. Their observations revolutionized our understanding of the brain and charted the course of neuroscience for the next century.
Our fundamental ideas about how the brain works have not changed in one hundred years since those images of nerve cells first came into focus in the late 1800s. Could our present understanding of the brain on a cellular level be as naïve as my understanding was that day when I looked in vain for the working parts of a calf's brain?
With 20/20 hindsight we can now see that the dazzle of electrical excitation in neurons and scientist's tight focus on the synapse, blinded neuroscientists to what should have been an obvious fact-only 15 percent of the cells in our brain are neurons. What do the other 85% of the cells, called glia (for glue) do?
Looking through their microscopes early anatomists saw that the nerve cell had peculiar structures designed to carry out their unique role in transmitting electrical information. The wire-like axon projecting from nerve cells and extending enormous distances to communicate with other neurons, was unique to the nervous system. The root-like dendrites sprouting from the opposite side of brain cells, which were originally believed to draw nutrients into the nerve cell to sustain it and power the electrical impulses, are special structures seen only in neurons. The true function of dendrites was soon appreciated by the great Spanish anatomist, Ramon y Cajal, (pronounced Cahall) who perceived that neurons communicate by sending messages across a gulf of separation between a neuron's axon and the dendrite of the next neuron in the circuit at a point called, the synapse.
The "Neuron Doctrine", as Ramon y Cajal's view came to be known, became the fundamental idea for our current understanding of how the brain works. All theories of information processing in the brain, and all of our drugs for treating mental illness, are founded on this one essential idea: synaptic transmission. The Neuron Doctrine tells us that all information in the brain is conducted by electrical impulses transmitted through neurons and communicated across synapses. But is this idea correct?
Now at the turn of a new millennium, a new kind of microscope is revolutionizing our understanding of the brain, and revealing a new dimension of brain function that astonishingly--operates beyond neurons.
Setting in a dark room at Colorado State University in the 1980s, crammed with computers and newly designed microscopes that grafted new digital technology developed for the booming video game industry onto the old optical microscopes, I first saw a neuron fire with my own eyes. Together with Stan Kater and Peter Guthrie, who were pioneers in this new method, we flipped a switch delivering electric shocks to a neuron and saw it emit a burst of light. The light was generated by a chemical we had introduced into the living neuron that fluoresced brightly when the nerve impulse forced calcium to flood into the neuron, driving a chemical reaction producing light. Previously neuroscientists had relied on microelectrodes to tap into electrical transmissions in neural circuits. Now using this new method, when a neuron fired we saw it light up as easily as one sees the pilot light illuminate on a TV when it is switched on. The first time we saw a neuron firing with our own eyes, our shouts of joy filled the dark empty halls.
This new technique fueled a flurry of research around the world using this new imaging method to study how nerve cells work, but very soon scientists were confronted with something completely unexpected and entirely beyond the neuron doctrine. Notably in the laboratory of Stephen Smith, now at Stanford University, but in many other laboratories as well, information was seen flowing freely not only through neurons, but through non-neuronal cells as well--glia.
How do glia communicate? What does this glial communication mean? What can glia, "the other brain" do beyond what the neuronal brain can accomplish?
We are rapidly learning the answers to these intriguing questions about the other brain. Glia communicate, and they provide a separate, non-electric network for information flow through our brain that operates independently but cooperatively with neuronal networks. Glia do not use electricity to communicate, so glia have no need for the axon or dendrites or synapses of nerve cells. Glia communicate by broadcasting chemical messages. Moreover, glia can sense information flowing through neural circuits and alter the communications between neurons at synapses! Glia, we now know, have receptors for detecting the flow of ions generated by neurons firing electrical impulses and for sensing the neurotransmitters neurons release at synapses. Glia intercept these signals and act upon them to increase or decrease the transmission of information across synapses and speed or slow the transmission of electrical information through axons.
These recent discoveries open an entirely new dimension into brain function. Glia are involved in all aspects of nervous system health and disease. They can control neuronal communication, development of the fetal brain, generation of new neurons in the adult brain, participate in epilepsy, Alzheimer's disease, mental illnesses such as depression and schizophrenia, and they provide a new mechanism of learning that operates beyond synapses.
I look forward to describing new research on glia in forthcoming articles together with the latest research on how the brain develops and is modified by experience. This is a new brain and new frontier.
1. The Other Brain, by R. Douglas Fields, published by Simon and Schuster, NY, 2009.
2. Beyond the Neuron Doctrine, by R. Douglas Fields, Scientific American Mind, vol. 17, June/July, 2006. p. 21-27.