Read The Root of Thought Online
Authors: Andrew Koob
Schiffer, D.
Brain Tumors: Pathology and Its Biological Correlates
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Tascos, N.A., J. Parr, and N.K. Gonatas. “Immunocytochemical Study of the Glial Fibrillary Acidic Protein in Human Neoplasms of the Central Nervous System.”
Human Pathology
, 13: 454–458, 1982.
As researchers scour the highways in the land that is our brain, they examine all the potholes and roadside trash as if it exhibits significant meaning. The baked and deteriorating pavement for the transport of electrical signals long distances was believed to contain all the information in the brain. Now, as researchers turn their microscopes and equipment to the astrocytes, the cities in this land, they are beginning to realize where the information in our brain lies and how it is created.
It has been more than 100 years since Cajal gave Golgi a beating in Stockholm. However, just because Cajal beat Golgi doesn’t mean he’s right. When Mike Tyson slaughtered Spinks and his ridiculous socks 20 years ago in 91 seconds, it didn’t mean Tyson had triumphed viscerally or that his boxing philosophy was some tenant of truth—it just meant he was the strongest. In the mid-1980s, glia was becoming understood to be much more important than Cajal’s brother Pedro thought.
However, at that moment in 1906, the year the forward pass was invented, a year after Einstein’s miracle year, the same year Sherrington coined the synapse, Cajal was strongest. He was a more dedicated scientist than Golgi at the time and displayed it with ironclad intelligence. Although he knew glia might have an important function, he saved his reputation for future generations by hanging his lame idea related to glia on to his poor brother Pedro—a despicable act by a controlling man. Golgi’s notion of a syncytium was completely obliterated and the Neuron Doctrine became the rule and the law. One didn’t question it unless they wanted to commit scientific suicide.
So astrocytes are getting their day in the sun now. Hopefully, researchers will find ways to treat diseases with the newfound renaissance in the world of brain science. The most abundant cell in the brain is no longer just putty, glue, or support; it is an active cell that contributes
to our thoughts. It is no wonder no cures exist for brain diseases when the most abundant cell in the brain was completely neglected for so long.
The neuron-glial dichotomy is like the chicken and the egg. What came first? It’s hard to know if you study only the egg. Maybe 100 years from now, when a person visits the neurologist or walks by the neuroscience department, she will ask why it is called neuroscience when our thought has been proven to reside in our astrocytes. The use of “neuro” will be a nice antiquated term and an interesting story, such as why Iceland is called Iceland and Greenland is called Greenland.
Besides the obvious implications in disease treatment, as researchers delve more into the astrocyte, another enormous implication is the understanding of consciousness, creativity, and imagination. The astrocyte is more abundant in the human cortex than in lower animals, and the astrocyte turnover in lower animals is known to occur in places such as the olfactory bulb.
The turnover of astrocytes might be the quintessential cornerstone for our human information storage. As the mouse needs to understand its environment through its nose, maybe humans have evolved to process information from all senses on a higher level and the astrocyte turnover in the cortex is an integral part of this processing. This might be similar to how the shark’s skin has evolved to increase its swimming speed, to make it a better killing machine as it slices through the ocean searching for a meal. What makes humans special is the turnover of astrocytes, the best on the planet evolutionarily for the understanding of the environment.
Human social behavior evolves when we break the barrier of time and understand the calcium flow in our astrocytes. Next time you come up with an idea or look at a piece of art, hear a good song, watch a fantastic movie or cartoon, think about where it burgeoned. A calcium puff sparked a wave through astrocytes in an area that possesses information corresponding to the framework of the creative idea. As you ponder what you imagine, more calcium waves flow, creating more astrocyte growth. When you decide to act on it, the astrocytes correspond with adjacent neurons and whoosh—off it goes down to your muscles.
The neuron web, like the Internet, zooms information electrically back and forth; however, information is stored in computers by people. Although information in the brain is sent quickly along neurons, the information is stored and controlled by the astrocytes.
Calcium is one of the most volatile ions on the planet. It is sequestered in compartments in astrocytes. The astrocytes receive information from the senses through the neurons and the waves of calcium ions flow from astrocyte to astrocyte. The calcium puff is the beginning of creativity, and the man behind the computer talks fluidly with other people like the calcium waves in the astrocytes, and information is sent again down the Internet.
Who knows? The root of thought might be in our electrons or protons or quarks or gluons. However, the cell needed to understand whether this is true is in the astrocytes.
We assume what we know is true, but how we know it might prove false. For instance, the notion started by Cajal that solidified synapses are how we learn might have little to do with the beginnings of information processing. When astrocytes determine the amount of synapses, the synapse number no longer becomes important except as a consequence of astrocyte activity. The fact that the synapse number is controlled by astrocytes means to study the synapse number without astrocytes is like studying soldiers in a war without trying to understand the motives of the generals and commanders.
Synapses are just exits off the neural freeway. Neuronal action is like sex with no foreplay. It alone involves reflex and base thought—just taking in sensory information without processing. Glia are the pondering cell—the cities where the information resides. The rumination over the senses and effective action gets done when glia tell the neurons what to do.
The secret murmurings in the back of labs about the pointlessness of neuronal focus have been coming out in the last 20 years in a few brave papers by fearless scientists. The repression lasted for so long because of the nature of the Neuron Doctrine. It had infiltrated every facet of brain science. Any class on the subject completely discounted the most abundant cell in our brain by saying that their role is “to support neurons.” Because of the money it takes to run a lab, research on glia became impossible. Funding wasn’t typically given out for glial projects, so there was no incentive to spend a large amount of time applying for a grant to study glia when it was obviously going to be rejected. Glia was seen as a waste of time.
The prevailing thought was that if the people in charge of funding want to hear about neurons, we’ll give them neurons. Following the latest trend in the neuron black hole could reward a researcher with a hefty grant to lure them down the path of Cajal servitude. Cajal ruled his world with a clenched fist long after he died.
Thankfully, this is changing and the Cajal grip is loosening. The secret that they won’t tell you in biology class is that at most brain scientists agree that glia are equal or more important than the neuron. Science can be a religion in certain aspects and all things believed today can turn out of favor tomorrow. There are an infinite number of avenues to pursue, shrouds to lift, and worlds to discover. Discovery is fun, good, and fantastic; however, no matter what we believe today, always somewhere below lies the truth.
It is good to be cautious about what is absolute truth. Science constantly changes as the equipment changes. It was difficult to study glia with the techniques available during the time of Cajal. It was also difficult to study neurons. However, with the discovery of electricity and the electrical body, more could be inferred.
It is astonishing that so much has been placed on the neuron. It is now blatant this focus has resulted in stunted knowledge of many aspects of human thinking and cures for human diseases. Because when something is discovered, it always leads to the next thing to be discovered. And that next thing might negate much of what preceded it. As brain science exists now, the dominance of the neuron is under review, and we can hope as the community focuses on astrocytes that it will be more fruitful in the understanding of brain disease and injury.
So enjoy the waves, but watch out for the sharks.
This book materialized from four places. The first one was a lecture by Dr. Arturo Alvarez-Buylla for Dr. Paul Collodi’s neuroscience seminar at Purdue University in the Fall of 2002. It opened all of our eyes.
Then, after sharing glial cell research ideas and lamenting the impossibility of glial cell research funding with fellow graduate student Peter Cormie over beers at Harry’s Chocolate shop on a random Tuesday afternoon while trying to avoid lab work, and more specifically the torture of rats, Pete said something when we were walking out of the bar after we had about five Guinness while listening to the entire Appetite for Destruction CD on the jukebox, “What if glial cells hold all the information in the brain?” And we both stopped in our tracks.
In the Spring of 2004, I was in the Las Vegas airport during the NCAA tournament. I was upset that the DePaul game went over, when I came across the
Scientific American
article “The Other Half of the Brain,” written by R. Douglas Fields about Einstein’s brain and glial cells. The article blew me away not just because of the subject but because of the way it was presented.
Lastly, while gathering information for this book, I noticed a recently published little green book called
Glial Neurobiology: A Textbook
, which is a fantastic resource by Alexei Verkhratsky and Arthur Butt. In the preface, they state, “In a way, the binary coded electrical communication within neural networks may be considered as highly specialized for rapid conveyance of information, whereas astroglial cells may represent the true substance for information processing, integration, and storage.” If you are interested in learning more about the glial cell, this book is the place to start.
First, I’d like to thank my wife, Lisa, who has been part of this from the beginning. It’s been fueled by chicken cutlets.
My parents, and especially my brother Alex, for checking out all the books at the University of Iowa. It’s his passion.
I would also like to thank my editor Amanda Moran. She is fantastic to work with and has been incredible throughout the whole process.
Thanks to my graduate advisor, Dr. Richard Ben Borgens, a wonderful combination of Mark Twain and Teddy Roosevelt and the perfect mentor. Dr. Borgens is someone who understands the art of science. His enthusiasm is unmatched. If it weren’t for him, I’d be out in a field somewhere left for dead.
I also want to thank Dr. Thomas Klopstock and Dr. Andreas Bender, for bringing me to Munich to work on fascinating projects, and suffering through times when my mind is out to lunch.
And special thanks to Jodie Rhodes, who was the reason this book materialized.
Andrew Koob
is currently researching brain disease at the University of Munich, Germany, where he continues to trumpet subversive glial theories. Previously, he has worked as a postdoctoral research fellow in pediatric neurosurgery at Dartmouth College and was a postdoctoral fellow for research in Parkinson’s Disease at the University of California, San Diego.
acetylcholine,
23
action potentials,
42
Adenosine-5-triphosphate (ATP),
50
adult neurogenesis,
84
alcohol
effect on astrocytes,
118
effect on mammillary bodies,
139
Aldini, Giovanni,
19
all-or-nothing phenomenon,
3
alpha-synuclein,
124–125
ALS (Amyotrophic Lateral Sclerosis)
identification of,
122
problems with glutamate transporters in,
126
Alvarez-Buylla, Arturo,
85
,
89–93
Alzheimer’s Disease
identification of,
123
link with apoE gene,
125
protein deposits in neurons observed in,
124–125
Alzheimer, Alois,
123
amphibians, ratio of glia to neurons in,
36
amygdala,
151
amyloid tau,
124
Amyotrophic Lateral Sclerosis.
See
ALS
angiogenesis,
147
angular gyrus,
104
anions,
44
aplysia,
83