The Root of Thought (10 page)

Haydon described the neuron-astrocyte-neuron action as the “tripartite synapse.” According to this theory, the neuron arrives with information to signal to the next neuron, similar to a waiter who delivers a meal to a customer, and the astrocyte adds salt and pepper to the dish. However, the tripartite theory does not take into account the ability of the astrocyte to signal to a neuron spontaneously, without responding to a neuronal stimulus. The astrocyte doesn’t just add salt and pepper; instead, it is the cook that prepares the meal.

Let’s say you want to punch someone in the face. Maybe the person told you to go to hell. Maybe he insulted your mother. Or, maybe you’re a firm believer that the Smurfs were better than the Snorks, and this joker is taking the side of the Snorks. Anyway, you are receiving some sensory stimulus that enters your brain. It reaches the cortex, and your astrocytes produce calcium waves in respond to such a strong stimulus as you process the stimulus of Snork dominance. Previous experience that has been solidified by the calcium astrocyte signaling reminds you that the Snorks suck. The frequency of the waves tell neurons to fire, which respond with you drawing back your arm and punching the poor dude right smack between his Snork-loving eyes.

This response can be so rapid that it acts as a reflex, bypassing astrocytes altogether. Astrocytes have been shown to shrink their cell body to let neurons fire to each other uninhibitedly. Their end feet relax and pull up, like a child on a big wheel going down a hill. The neurons are allowed to fire rapidly without interruption or influence to create a reflex without the inhibition of thinking.

The processing of astrocytic calcium waves takes much longer than neurons. They might be primed at the synapse for a Smurf-Snork debate because you have thoroughly thought about this subject. Astrocytes at the synapse when you hear “Snorks are better than Smurfs” simply redirect this to your motor cortex for the arm movement of a punch.

In fact, pondering anything intensely, such as cartoons over many sittings through the course of many Saturday mornings, can lead to the point that you drown out all sensory stimuli while considering the question. This original thought might be entirely astrocyte-driven through calcium waves.

Where do original thoughts and ponderings come from? Where does a revelation come from? If the astrocytes are placed with neurons in culture, spontaneous calcium signaling in astrocytes can not only cause calcium waves, but these calcium waves can also cause neuronal signaling to occur. This can explain how we can vocalize our imagination. Where did George Lucas come up with the idea to clothe Darth Vader in a black plastic helmet of that design? Did the apple that hit Newton’s head coincidentally spur an astrocyte calcium signal from a puff to a wave? One could say Proust’s
Remembrance of Things Past
is one long calcium wave flowing through his cortex. Let’s not even get started on where Jim Henson’s creations spawned from. Spontaneous calcium signaling and the subsequent neuronal firing could be the act of creation. Spontaneous calcium waves would also flood over astrocytes that store information based on our previous experiences, thereby influencing our creation.

When neuronal firing is blocked, calcium signaling continues in astrocytes. These splashes of calcium waves without neuronal influence might be considered the wild imaginings and dreamlike state of a person in a sensory deprivation tank or the random dreams integrated by calcium flow during neural shutdown.

It has also been discovered that all transmitters not only act on astrocytes, but when they are released by neurons, they can also be transported into astrocytes, where they are broken down and resynthesized. This has been shown to be the case for all transmitters: glutamate, dopamine, serotonin, and so on. However, what happens to these transmitters when they are formed again in the astrocyte was not known until a decade ago.

It was discovered that glutamate released from astrocytes might be the same glutamate that is taken up from the extracellular space when released by neurons (or astrocytes). Glutamate is then released in the same manner from astrocytes that they are in neurons.

Glutamate exists in astrocytes at a concentration between 10–10,000 fold higher than the extracellular space. As is the case with ions, this incredible difference can cause a gradient, where if one room is cold and the neighboring room is hot, when you open the door, the hot air will rush in and the temperature between the two rooms will even out. After a calcium wave enters an astrocyte, the trigger sends glutamate in small membrane balls to the cell membrane, where the balls fuse and glutamate is released into the extracellular space.

To transport glutamate into an astrocyte, two or three sodium ions and one hydrogen ion come in as well, with outward movement of one potassium ion. Glutamate transporters that shuttle the transmitter into the cell during this ion exchange are highly expressed in astrocytes. The stockpiling of glutamate continues until the floodgates are opened.

Other than glutamate, astrocytes have also been shown to release almost every other kind of transmitter. Astrocyte receptors at the synapse correspond to the type of neurons they are near. If the astrocyte is in the cortex, it will likely have glutamate receptors. If it is in the basal ganglia, which is damaged in Parkinson’s disease, the astrocytes will respond to dopamine.

There is evidence that channels at the gap junctions (places where astrocytes connect to one another) release glutamate and transmitters from astrocytes as well. When the wave enters the gap junction, glutamate can drip out. However, the function of this channel release is not known.

Release of transmitters from astrocytes is different from neurons in some aspects. Researchers have examined this by using toxins. Toxins, such as tetanus toxin, which can completely stop transmitters from neurons at the synapse by blocking fusion of the small membrane balls within minutes, can block only about 70 percent release of transmitters from astrocytes after 20 hours. This is likely because the astrocyte has many other avenues of transmitter release than neurons. However, botulinum neurotoxin A (Botox) can block astrocytic release of transmitters more efficiently. The lesson is: Don’t inject Botox into your brain; you might have trouble thinking.

In the cortex, a single astrocyte lords over the environment surrounding it. Astrocytes control nourishment from the blood. Astrocytes release transmitters at the synapse to control neuronal firing. They not only receive information from neurons, but also imbibe the transmitters released by the neuron. An astrocyte can even dictate the type of signaling it wants a neuron to perform. Neurons have the capability to fire at different frequencies. Studies have shown that short signaling can increase, whereas longer ones are suppressed when a particular astrocyte signals at the synapse.

In the hippocampus, which is the area of the brain responsible for forming new memories, about 80 percent of large synaptic contacts are surrounded by astrocytes. As information comes in from the senses through neurons, calcium waves responding to neuronal firing in the hippocampus move at frequencies comparable to the firing of the neuron. The waves also do not spread unless the strength of the neural firing is sufficient. It was formerly believed that memory formation in the hippocampus resides strictly in neurons. However, calcium waves become more frequent and are more easily initiated if the neuron in the area had previously fired strongly. Strong firing at a synapse indicates that a strong stimulus comes from the senses. Strong firing increases the capability of this axon to fire the next time it is stimulated. However, in astrocytes, a strong stimulus from neurons also increases the frequency of calcium waves, which spread to all adjacent astrocytes. Formation of memories is in the hippocampus, but information resides throughout the cortex. This is the domain of the astrocyte. The stimulus from the senses creates a better road to travel through, a freeway, in the form of a neuron. But the information is processed and resides in the astrocyte.

If someone tries to remember something through repetition, the sensory stimulus of the person repeatedly saying what he needs to remember is fired into the hippocampus. For instance, you are out at a bar and meet a girl named Jenny. You are having a good time with her, but she has to leave, so you try to get her number. The only problem is no one has a pen to write it down. So you repeat the numbers several times—867-5309, 867-5309, 867-5309—to solidify the memory. When you get home, you try to remember—what was Jenny’s number? The neural signal fires into your brain as you repeatedly say the number, stimulating astrocytic calcium waves, which increase in frequency because of the repetition of the earlier neuronal firing. Or, you could just put the number in your cell phone.

In calcium wave firing, as each wave rises, a shot of glutamate is released from the astrocyte. An increase in calcium waves results in an increase of glutamate release. This transmitter signaling to neurons doesn’t occur strictly at the synapse. Astrocytes can influence the neuron at any point along its beautiful long body. As waves spread to other astrocytes via gap junctions, the other astrocytes will release glutamate and stimulate more neurons in their area. One astrocyte also contacts dozens of cells, releasing glutamate and spreading calcium to all of them.

Not only are astrocytes the cells where thoughts and memory reside, but they can also contribute to our body’s hormonal levels. Astrocytes produce proteins in areas of the brain concerned with water homeostasis and microcirculation through the brain. These proteins are called vasoactive intestinal peptide, atrial natriuretic peptide, and brain angiotensinogen—three names you won’t see on a law office. They influence neurons that release hormones into the blood. The hypothalamus has neurons that can secrete hormones into the blood as well.

Hormone secretion is influenced by glial cells in the area of whole body fluid balance. Glial action on neurons causes the release of vasopressin and oxytocin in the blood, hormones directly responsible for regulating whole body fluid.

Astrocytes can also change the synapse’s appearance. Acting like water to plants, the astrocyte rains on the neurons and helps them grow. Without astrocytes, the neurons are stunted and produce few connections. Similar to dried-out crops during the desert wasteland of the dustbowl, neurons sit brittle and pathetic in their Petri dish, forlorn and sad entities. They are probably crying. Your heart goes out to them.

However, throw down some astrocytes beside them and everything blooms, as though ET has pointed at them. The amazing transformation is due to the capability of astrocytes to influence axon outgrowth. Astrocytes can also cause neurons to form many more synapses. Neurons in culture by themselves form few synapses and are immature. Astrocytes build roads for their long-distance information transfer.

Mauch and colleagues in Frank W. Pfrieger’s lab in Strasbourg, France in 2001 were able to isolate the molecule responsible for the increase in synaptogensis. They were not anticipating they would find this all-important molecule to be cholesterol. Astrocytes have the capability to synthesize cholesterol and release it from their cell bodies.

Astrocytes maintain a synapse simply by their presence, which strengthens the connection through signaling of transmitters and growth factors. It has also been shown that glia have the capability to eliminate synapses. Apparently, when a synapse has fallen out of favor, it is torn out like a railroad track no longer in use.

If neurons require this much maintenance from astrocytes, how can they be behind our motivations and thoughts? As human beings, an animal on this planet searching for food and procreation, we have sprouted evolutionarily out of some control of the elements of our surroundings. The volatile calcium ion, which is the integral element in cell-to-cell signaling in all organisms, might just be the haphazard chance fount from which organic life exploded. And calcium flowing in waves is the main signaling mechanism behind glia, the cell that is the most abundant in the brain and the cell whose ratio increases up the evolutionary ladder, taking a special place in the brain of human beings in the form of the astrocyte.

As scientists slowly come to the realization of the folly of 100 years of naming everything in the field after the neuron, they do it with their astrocytes.

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Imagine the earth slips through a rift in space and time and comes out the other end into a completely different universe. Imagine this experience coincides with all the blueberry bushes in the world growing 1,000 percent more blueberries. However, the blueberries look different; they have sprouted arms stretching over and around the bush and they are controlling the branches. Then the blueberry bushes get up, walk around, and talk, creating blueberry bush societies. Now, imagine you are a botanist who specializes in blueberry bushes and you want to kill one to find out how the blueberry bushes suddenly became so smart. Where would you study first—the branches or the numerous odd-shaped blueberries that suddenly grew and are now reaching around and controlling all the branches?