The Root of Thought (9 page)

The reason for our existence might be the control of calcium, and the abundant astrocytes in the human brain and ability for human communication might be the best expression of this control on the planet. Calcium can affect short changes in astrocyte signaling on the order of milliseconds. It can also change the makeup of the cell to respond to stimuli in a manner that lasts for months or years by binding on genes and proteins and changing their functions.

Calcium waves in astrocytes spread much slower than neuronal communication and is a wonderful way to integrate and process information. It does not take a leap of faith to think astrocytes receive information from fast-acting sensory neurons to store the information for long-term use. In turn, they communicate to neurons when we need to create muscular action or send information to astrocytes in other parts of the brain.

Calcium is hard to sequester because its reactivity with other molecules is so volitale. The spontaneous release of calcium waves from internal stores in astrocytes are intermittent and fluid—like raindrops falling on a lake. These calcium puffs, if strong and persistent enough, can also ignite calcium waves through the astrocytes. If calcium waves in astrocytes influenced by neuronal communication from the senses is us pondering our environment, spontaneous calcium puffs become waves in our moments of inspiration, creativity, and imagination.

Golgi imagined a similar way that we think. Although he imagined neurons, it is becoming clear his ideas are real in astrocytes. Astrocytes are a physically intertwined net with cells in their surrounding environment recruiting more astrocytes and storing information via the calcium wave and changes in calcium signaling. When neurons are introduced, the waves synchronize. Our ability to retrieve information in our brain is likely the grasping of astrocytes by sensory neurons.

Poor Cajal had no idea; although he had his doubts about the notion that glia are unimportant, he clung to his legacy and perceived brilliance by marginalizing the role of astrocytes to support. He was blameless because he hung it all on his poor brother Pedro.

With arms on blood vessels that can increase flow to areas of thought, the astrocytes are activated, illuminating information in the depths of our existence primed to be retrieved for years, months, or minutes. If it seems necessary to act on this information based on the sensory stimulus in our presence, well, send it down the neurons.

The spontaneous activity of calcium in astrocytes might be the nature of our creative and imaginative existence as human beings. Never-heard-before thoughts arising for the first time out of the infinite possibilities. And a wave can flow over, releasing stored information of astrocytes able to solidify those thoughts. The progression of human existence could rely on the calcium, if the original thought is something worth learning by the other astrocytic populations. As the wave flashes through gap junctions, it recruits other astrocytes based on how their calcium release responds as a result of previous calcium signaling.

Surfers know waves are finicky things; some days, waves come in large and forceful in sets of three or four interspersed with lulls, and other days bombarding the beach in sporadic swells. Some days, when the wind is high, they are impossible to navigate because of the choppiness. Calcium waves in the living human brain are something researchers are unable to study directly, but that day is coming. It is known that they can likely be synchronized, like the nice sets surfers lust after. It is thought that they can be more sporadic and unpredictable when they are sitting idly. No matter how astrocytes are influenced—chemically or through changes in blood flow—our imaginations are fueled by such subtleties.

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Draped in astrocytes, neurons witness the calcium waves flowing throughout the cortex. However, they are not innocent bystanders. As the calcium wave breaks and spreads to other astrocytes, it is returned and sequestered back to the internal stores in the cell. But we are not in
A Clockwork Orange
—sitting in chairs with our eyelids peeled open as subjects of experimental aversion therapy. We act on what we experience. Astrocytes process the information coming from our sensory neurons, and in some cases, after communicating with each other, astrocytes might decide to act on our motor neurons, unless we are embroiled in a DVD marathon of course.

Astrocytes are the root of our cognitive function, and therefore, are intertwined in our notions of survival. Maybe their processes, called ”endfeet,” extend out attaching to our blood vessels and tell us we are thirsty. Astrocytes might decide to pick up a glass of water.

We know calcium is released from internal stores in astrocytes. After it is released, it moves in a wavelike fashion to other astrocytes through gap junctions that enable astrocytes to communicate. This process might be how humans store and retrieve information, create new ideas, imagine, and make decisions.

We also know astrocytes express receptors for every type of transmitter released from neurons. Transmitter action on astrocytes can cause calcium waves to occur. And now we know that an astrocyte can tell a neuron to fire.

In his paper with Stephen W. Kuffler (1913-1980) on the nature of neuron-to-glia communication, Richard K. Orkand states, “The magnitude of the potential fields and their influence on neighboring neurons created by the glial potentials is not known. Available experiments do not support the idea that currents in glial cells influence neurons because the
clefts greatly attenuate current spread between the two cell types.” However, in 1990, Harold Kimelberg from Albany Medical College, in an attempt to understand the swelling of astrocytes in brain injury, cultured cells in a Petri dish and added factors that caused them to become impregnated with fluid. This swelling resulted in transmitter release from astrocytes.

Then, in 1994, two papers came out independently of each other and almost simultaneously, in the journals
Science
and
Nature
, that showed for the first time astrocytes communicating to neurons.

Philip G. Haydon’s lab at Iowa State University and Maiken Nedergaard at Cornell University studied the calcium action of astrocytes in relation to neurons. In culture, Nedergaard stimulated a single astrocyte and watched the calcium waves emanate to other astrocytes in its vicinity. However, she also noticed that calcium increased in the cell body of the neuron next door—a phenomenon that causes transmitter release.

Haydon’s paper, by Vladimir Parpura and colleagues, took it one step further and studied the action of glutamate. Glutamate is an excitatory transmitter prevalent in the cortex and previously thought to be only released by neurons. They show that glutamate could be released from astrocytes and cause signaling in neurons. The implication of glutamate release from astrocytes to act on neurons was revolutionary in the mid-1990s. This was as outrageous as hearing that the Pope faced Mecca on his knees every day. The first notion that glutamate had anything to do with astrocytes at all was in the mid-1980s.

In 1984, Helmet Kettenmann and colleagues at the University of Heidelberg showed that the transmitters glutamate, aspartate, and GABA cause electrical potential changes in astrocytes. Changes in electrical potential in astrocytes without action potential had been known since Kuffler. However, no one believed that a transmitter could act on astrocytes. They were called “neurotransmitters” after all. Then, when Murphy and colleagues threw some glutamate on astrocytes in the mid-1980s, the subsequent understanding that a transmitter released from neurons could produce a calcium wave in astrocytes blew everyone’s mind.

The revelation that glutamate can act on astrocytes led to the discovery of glutamate receptors on the astrocyte membrane. The state of the importance of the neuron and the Neuron Doctrine was so influential that glial cells were the last cells in the body that were discovered to have receptors. Researchers exhibited that human trait of overlooking thought to submit to the will of the more powerful and accepted Cajal for fear of losing their livelihoods or being brandished as crackpots. This detestable assumption of glia being insignificant at the submission of Cajal’s intellect led to the most abundant cell in the brain being the
last
cell looked at for receptors. Receptor signaling is ubiquitous throughout the body in all cells. However, in the brain it was thought to only be the domain of neurons. Thinking about the cells of thought was repressed!

The electron microscope pictures from the 1950s onward show the close proximity of astrocytes to neuronal synapses. Researchers were unsure what to make of the junction between these highly electrical firing cells being probed by worthless astrocytes. Sherrington and Cajal would have rolled over in their graves. The silver stains produced by Golgi and Cajal showed a different astroycte, set apart from neurons, in beautiful glory. However, the silver stain doesn’t stain all cells, just a few. Microscopes weren’t powerful enough to consider the level of cell-to-cell snuggling. Outside the axon, to bear the brunt of an electrical pulse made sense for astrocytes; however, probing like a nosey neighbor into the domain of the neurotransmitter did not make sense. This synaptic contact and subsequent discovery of glutamate-induced calcium waves in astrocytes indicated that astrocytes might process information at the synapse.

When Phillip G. Haydon, Vladimir Parpura, and colleagues found that astrocytes had the capability of releasing glutamate into the extracellular space in a similar manner to neurons—and then subsequent separate studies showed that astrocytes could cause an actual action potential in neurons—the neuron, in all its glory, was being told what to do.

One could look at this as “neurons also tell glia what to do” because of astrocyte expression of transmitter receptors. This is true. However, the nature of neuronal firing ties it to sensory or motor function, signaling from the senses and transmitting to the muscles. The astrocyte has no such attachment. The astrocyte processes neuronal signaling and instigates the rapid action of neurons to muscles and the viscera. This idea can be better understood by thinking of a photograph or video. When a director films a movie, the image she points the camera at is imprinted on the film. The film can be played back to recreate the image. However, you wouldn’t say the film is the director. In
Figure 6.1
, astrocytes are the
processesors of sensory information and the instigators of motor action using neurons as tools. As will be seen in later chapters, astrocyte growth can be achieved through more attention and concentration or focus by the human mind.

FIGURE 6.1 The astrocyte processes and retains information from the senses, and it tells neurons to fire for action.