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Practitioners of the Neuron Doctrine claim that the trillions of connections are sufficient for the construction of thought. However, a cellular breach between sensory and motor function is plausible. It would seem the sensory input to the brain might be processed by astrocytes and astrocytes then influence motor action based on the sensory input attained, whether the motor action is speaking, lifting your arm, making love, or something else. Simple reflexes to frightening or exciting stimuli
bypass the astrocyte. It can be seen as a balancing fulcrum, where one side is a sensory-dominated animal soaking in its environment like a sloth barraging an indifferent astrocyte, an obese dog on a porch in the sun watching the cars go by, or a motor-dominated animal, running about like a chicken with its head cut off. An astrocyte expending energy without thoroughly considering its environment is like a yippy dog chasing its own tail. In the middle are balanced motor and sensory stimuli with astrocytes receiving input, signaling to each other and controlling motor output.

An astrocyte is a self-sufficient, self-replicating cell signaling to itself contentedly. Neurons have no reason to exist except to support astrocytes. Mature neurons cannot function alone, whereas mature astrocytes have no difficulty existing without neurons. When placing mature neurons in a Petri dish, they are unable to survive without astrocytes. Astrocytes are perfectly content without neurons.

Cajal’s contributions to the foundations of neuroscience are undeniable. However, the fact that the field is called “neuroscience” illuminates his overpowering influence and the knee-jerk studies of some subsequent researchers. Cajal’s intuition told him that glia were likely more prominent than believed, as betrayed by the way he scoffed at Carl Weigert’s suggestions that they were merely space fillers with no function at all. With the techniques available to Cajal at the time, he didn’t believe he was able to study the astrocyte. However, his powerful conviction of neuronal prominence set back studies on the most abundant cell of the brain area responsible for higher thought.

The Neuron Doctrine explored throughout the twentieth century is the basis for how we understand our brain, but it completely negated for nearly a century what might be the most important cell in the brain. As with any doctrine or regime, any detractors were summarily discounted or laughed at. You certainly did not tell Joseph McCarthy communism “isn’t such a bad thing” in the 1950s. You didn’t tell the inquisition that Martin Luther “was a decent dude.” And you definitely did not tell a brain scientist in the twentieth century that the astrocyte was more important than the neuron. However, the mounting evidence is too glaring to overlook, and the astrocyte might prove to be the reason for neural existence.

References
 

Fedoroff, S. and A. Vernadakis.
Astrocytes: Cell Biology and Pathology of Astrocytes
, Volume 3. San Diego, CA: Academic Press, 1986.

Gerhart, J. and M. Kirschner.
Cells, Embryos, and Evolution
. Malden, MA: Blackwell Science, 1997.

Hebb, D.O.
The Organization of Behavior: A Neuropsychological Theory
. New York: John Wiley & Sons Ltd., 1949.

Kettenmann, H. and B.R. Ransom.
Neuroglia
, Second Edition. New York: Oxford University Press, 2005.

Laming, P.R., E. Syková, A. Reichenbach, G.I. Hatton, and H. Bauer.
Glial Cells: Their Role in Behavior
. New York: Cambridge University Press, 1998.

Murphy, S.
Astrocytes: Pharmacology and Function
. San Diego, CA: Academic Press, 1993.

Papper, S.
Sodium: Its Biological Significance
. Boca Raton, FL: CRC Press, 1982.

Ramón y Cajal, S.
The Neuron and the Glia Cell
. Springfield, IL: Charles C. Thomas Publisher Ltd., 1984.

5
Riding the calcium wave
 

Evergreen-shaped neurons, processing information with electrical sparks flying about and crackling our skulls is the current popular held belief of our brain activity. This militaristic science of the brain, with neurons firing like guns and bombarding our brain in the form of thoughts, has been under review for a couple decades. Since the 1980s, scientists discovered the smooth flow of calcium oscillations or waves. Some might think this is the advent of surfing as a popular sport, the unregimented flow of riding waves displacing the arms war of football, and the heaters thrown by pitchers in baseball. If you’ve been in the military and you’ve surfed, it’s much more likely that your brain works in the manner of the waves. They are even rough in the winter, like the mood of a man, and the flow of waves in surfing might have a subversive effect on neuroscience research. When the movie
Gidget
came out in 1960, surfing became the rage, and soon afterwards, Steven W. Kuffler’s lab was the first to take a serious experimental approach to the glial cell.

If astrocytes are the mediators between sensory experiences and motor action—the black box where imagination and creation occur—they must be able to communicate among themselves. Weigart’s concept of a static, dull astrocyte contributing nothing to brain function except as a space-filler, like the feng shui placement of a seldom-used dining room table is now defunct. And Pedro’s notion of glia as simply a buffer zone for excess electrical neuronal electricity is being turned on its head.

There is no need to put a pointless aesthetic table in the middle of a spacious house, with no functional purpose—just as there is little possibility that the most abundant cell in the brain sits there doing nothing. Only elitist scientists at the turn of the century would think of this crackpot idea for a brain cell, possibly with so many unused tables in their own
homes. Glia are not glue or inconsequential space; it is now turning out to be the exact opposite. Rodin’s thinker was certainly using his astrocytes, and Myron’s discus thrower was using his neurons.

For the astrocyte to be the root of thought, it must be able to process sensory information coming from neurons. It must also be able to communicate to motor neurons to stimulate action. In the peripheral nerves, electrical impulses rapidly fire through sodium and potassium exchange to the muscles to cause contraction, electrical impulses we know as “action potentials.” Action potentials also carry information pertaining to sensory input from the body to the brain.

As the physiological techniques developed to study electrical communication in nerves, scientists began to use these techniques on glial cells in the late 1950s and early 1960s. As scientists stuck electrodes into the cells, they initially believed glia had no electrical potential. They were just sitting there like a piece of wood—something to knock on for good luck. However, these studies were performed inaccurately and were more designed as a confirmation of Cajal’s conclusion—the platitudes of yes-men trying to please their revered ancestors.

In 1955, Paul Glees (1909–1999) broke from the neuron religion—and was the first to suspect a noninsulating role for astrocytes. Glees wrote a book titled
Neuroglia: Morphology and Function
and stated, “Apart from a protective, insulating and supporting function, could neuroglia have a metabolic activity exceeding its own requirements, which would influence directly neuronal metabolism or synaptic activity? Until this dynamic concept has been proved, neuroglia will remain largely a domain of morphology and the artistic delight of neurohistologists.”

The first studies of the physiology of glial cells in vertebrates were performed on the frog and mud puppy and published in 1966 out of Steven W. Kuffler’s (1913–1980) lab at Harvard. Ironically, in the same year, he founded the Harvard neurobiology department. The name of the department demonstrates the influence of the neuron doctrine through the twentieth century. If he were more democratic and more aware of his research, he would have called it the “Brain Biology Department.” Of course, this doesn’t sound as fancy. Kuffler’s groundbreaking studies were also performed with the intent to provide evidence for Pedro’s theory, but he inadvertently discovered an electrical potential in astrocytes along the way. At the time, it might have been more appropriate for him to call the department “The Neuro and Check Out This
Random Interesting Stuff We Found Out About This Previously Thought to Be Functionless Cell Department.”

He starts the mud puppy paper with the line, “Little is known about the physiological properties of glial cells in the vertebrate central nervous system.” In fact, in 1966, absolutely nothing was known about glial cells, the most abundant cell in the brain by a large magnitude.

The studies that Kuffler and his students Nicholls and Orkand performed on the leech encouraged the idea that glia were functioning cells. In science, however, since humans are vertebrates and not octopi, a paper on a leech matters less than one on a vertebrate. In the frog, as in the leech, they found astrocytes exhibited an electrical potential that could be changed dramatically in the presence of potassium. Kuffler was interested in potassium as it flows out of neurons during an electrical potential. He wanted to test (or confirm) the theory that glia absorbs neuronal electrical firing, and the idea that astrocytes respond to potassium might lead credence to the theory.

The finding that astrocytes respond to an ion had long-range implications and inspired scientists to consider them more closely. Electrical stimulation of astrocytes was unable to create an action potential, however, and because this was believed to be the only worthy brain cell communication (the preferred method of the neuron) scientists could not yet grasp the importance of glia.

In an adjoining paper, when Kuffler and colleagues stimulated neurons, they found that glia also depolarized. They assumed that potassium influx in glial cells was the main constituent of this depolarization. However, scientists now know that many factors contribute, with calcium taking the most prominent role.

In 1986, Sean Murphy and colleagues at the Open University discovered that transmitters released from neurons stimulate astrocytes in the neocortex of rats and cause calcium influx. The known behavior of calcium as a cell regulator of communication gave pause to researchers. The year after Kuffler’s research on glia, calcium was shown as necessary at the synapse in neurons to release transmitters.

Like sodium and potassium, calcium is also a prevalent oceanic ion and likely had an active role in the original formation of life. Although it was shown that extracellular sodium and intracellular potassium conduct an electrical pulse down a nerve, calcium wasn’t believed to be biologically relevant until 1883. Like most research in the eighteenth and
nineteenth centuries (and Kuffler’s lab), the story centers on the poor torture of frogs. Sydney Ringer (1836–1910) discovered that a dissected frog heart suspended in sodium would stop beating. When suspended in a blood mixture, the heart would continue to beat. But after removing the blood and then adding a saline solution, it would stop, first growing weaker and then halting after 20 minutes. After this time period, the heart would also not respond to strong shocks.

Adding potassium chloride or bicarbonate of soda to the saline solution would not help the heart to beat. However, when adding calcium, Ringer found the heartbeat could be maintained for four hours. Like most major biological leaps, his discovery occurred completely by accident. Ringer had his student prepare the mixture and instead of using distilled water, the student mistakenly used tap water. When Ringer discovered the calcium element in London tap water was equivalent to the amount of calcium circulating in our blood, he was able to perform the famous experiment.

The emphasis on sodium until that point was largely for obvious reasons. When we go to a lake and take a swim, we taste the cool fresh water that sometimes stimulates our thirst, but if you take a person from the middle of the United States, and put him on a beach in California, he might get the urge to go swimming in the ocean. If you don’t tell him what will happen when he tastes the water, he will come up spitting and gagging because of the massive salt content. However, we don’t taste calcium. In fact, we are incapable of tasting calcium. Sodium is the ion that is transmitted on our taste buds, and it was believed to be the most important ion because of its domination of the oceans. But sodium is tame compared to calcium.

Calcium highly reacts with the elements nitrogen and oxygen and the water molecule, which are prevalent in nature. It is speculated that the control of this abundant highly reactive molecule is integral to life. In the environment, calcium is mainly combined with chloride and carbon or other anions (negatively charged ions, which have more
electrons
in their
electron shells
than they have
protons
in their
nuclei
) in the form of a salt. Like a game of Tetris, the volatile calcium ions are stacked together to create organism structure. In bones and teeth, it is deposited as calcium phosphate. Seashells are mainly calcium carbonate.

Life apparently started on this planet about four billion years ago. As multicellular organisms evolved, calcium signaling and communication is believed to be the way cells were able to control other cells and themselves. The evidence for the role of calcium in the organism was left as footprints in the form of fossilized bones.

All beings today use calcium as a cellular regulator in all bodily organs. Calcium is extremely important in development. When an egg is fertilized, a calcium wave through the ovum initiates conception. Cellular development and division are calcium-dependent processes. Without calcium, an embryo will not develop properly and die. High concentrations of calcium are in a mother’s milk (among many other things).

In plants, calcium activity contributes in a similar manner. Root growth is stunted and useless if calcium is not present. In animals and plants, cell interaction and adhesion to each other, for an organism to actually be “multicellular,” requires calcium. A calcium signal tells flowers to bloom (see
Figure 5.1
).

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