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Authors: Andrew Koob

The Root of Thought (18 page)

Our experience in a sensory deprivation tank is more evidence for the sporadic calcium waves. Our thoughts are dreamlike, moving through surreal experiences unchecked by the outside world. This occurs with inactive neurons. Astrocytic waves flowing and crashing in our skull are responsible for this experience.

The extent of dreaming in other species is unknown. However, anyone who owns a dog who has heard the dog growl in its sleep knows that dogs sometimes seem to dream. The way the ratio of glia to neurons in the human being, the abundant astrocytes in the human cortex, and our more complex behavior could mean our dreams are more complex. However, this idea might seem attractive because we are human.

We are just tall bald bipedal rodents, our smooth bodies prancing around the planet like upright terrestrial seals. We have so much shame around our fellow species we go about gashing other animals with bloodthirsty zeal for their pelts with which to clothe ourselves. For centuries, we strutted around in rotting carcasses. Our evolution to use tools that propelled us to the top of the food chain might have simply been due to our inherent lust to massacre other animals to quench our intense desire to cover our genitals with their hides. And we sit in chairs made of cow, full of conceit at the notion of the superiority of our ideas. The thoughts of other animals almost certainly have to exist on a higher plane. If we knew how they contemplate the hominid, we would perhaps not be flattered. Then again, human beings might think on a higher level than other species. For the purpose of this book, let’s just imagine that’s true.

Our passive imagination, while sleeping or in sensory depravation, is a different experience than our active imagination. When we are awake and not in sensory deprivation, we also have the ability to exclude our senses. We can put ideas through logical progressions, which might illuminate a new idea related to what we already know. Or, we can ponder, wonder, and ruminate. Something can dawn on us. This is called daydreaming for a reason. It is the act of excluding the environment around us to focus on thoughts. Daydreaming is integral to the human experience and likely occurs in astrocytes. Active thought occurs at the bond between astrocytes and their connections to blood vessels. Like flexing a muscle, we can increase blood flow to our brain to nourish the calcium waves flowing to a moment of inspiration, a moment that might require us to instigate neuronal action.

The façade of dreams—macabre or wonderful, heightened thoughts, illogical, yet somehow touching on the most true and exciting elements of our nature—all reside in the abstract human mind, outside the straight-forward thinking of the practical awake, working, active, and talking person. Every night your regular normal self enters into your own psychotic world. Some people are forced to deal with this experience even while awake in the form of mental disorders.

Although most of the work related to psychiatric disorders has been geared toward the belief the problem resides in neurons, now that researchers have shifted their focus on glia and astrocytes, it should soon become obvious it will open many doors, which might illuminate the cause of these diseases.

The variegated and complex study of psychiatric disorders—as they relate to the core of human existence, our thought, imagination, and creativity—are perfect avenues for the study of astrocyte function. A study will likely reveal many astounding discoveries in the next century. Our astrocytes are who we are, and the processing of each individual must vary in some aspects. How they vary and why will be interesting to understand. One treatment that has been used for psychiatric disorders involves the long-standing relationship between lithium and bipolar disorder, formerly called manic-depression. Lithium is used as an ion to take the place of potassium and calcium, which are both ions prevalent in astrocytes. The stabilizing feature of lithium and other bipolar treatments often leads the patients to feel like “they are not themselves” and somehow have blunted their sharp existence; lithium just ain’t calcium.

Also, while studying the post-mortem brains of the clinically depressed, researchers noticed the reduction in the number of cortical astrocytes when compared to the brains of people who were considered normal.

In depression, the paucity of astrocytes might likely result in the relatively few calcium waves to stimulate proper areas. The thoughts of a person might be uncontrollable, sending them into the depths of the pointlessness of existence. Whereas in mania, the calcium waves are too fluid and intense—an ocean in a hurricane state—resulting in extreme active behavior and euphoria.

Reduced numbers of astrocytes have been seen in the brains of people who have schizophrenia. The study of schizophrenia could be greatly
helped if more was understood about the disorder as it pertains to astrocytes. Disruption of serotonin, the transmitter believed to be responsible for mood, has also been reported in schizophrenia, and the action can be similar to what occurs while taking hallucinogenics. Schizophrenics are well known for their wild hallucinations. This serotonin influence causes astrocytes, which receive input from the senses to be in calcium wave activation without being stimulated by neurons.

Treatments for depression are commonly serotonin reuptake inhibitors. The theoretical idea being that serotonin is allowed to stay longer at the synapse and act on neurons for a longer period of time. Serotonin reuptake is performed by astrocytes as well, and the effect might be to stimulate receptors on astrocytes by continuing release of internal calcium stores via this pathway. Activating more astrocytes when the numbers are depleted might be the reason for the effects.

One uniquely human experience is the conscious decision to take mind-altering substances. The role of astrocytes in the processing of recreational drugs has not been adequately studied due to the relatively recent understanding of the prominence of glia in brain functioning.

However, because astrocytes express receptors and reuptake transporters for transmitters, it is believed that drugs acting specifically on transmitter receptors can instigate astrocyte activity and communication. Nicotine is known to act on the acetylcholine receptor and caffeine on the adenosine receptor. These receptors have been shown to be expressed in glial cells.

The mechanisms of withdrawal is believed to occur because constant activity on the receptor causes the cell to produce less of the receptor, which leads to a period of withdrawal symptoms off the drug where cells cannot signal as robustly until their receptor numbers are increased again. In the last 15 years, research has shown that heroin can stop cellular genesis. It seems morphine might be able to repress the action of cellular genesis, the unique process of the astrocyte. The lowering of astrocyte numbers without transmitter increases, such as serotonin, has been linked to depression. This method of depression could be the experience of withdrawal symptoms.

Just recently, exciting new research on glia from Alfonso Araque’s lab has ironically come from the Cajal Institute in Madrid, named for the biggest neuronal proponent of them all, Ramón y Cajal. Araque and Marta Navarrette are giving insights into the action of marijuana on
calcium waves. Marijuana has been used for a long time in human history, and the activation and mechanisms of the drug in the brain were finally described in the early 1990s. The tetrahydrocannabinol (THC) in marijuana mimics transmitters, which have been called endocannabinoids. Because the original research was neuron-centric, endocannabinoids were shown to work as a feedback mechanism in neurons, released by a neuron to act backwards on the one that just fired to it. However, just recently it was shown that endocannabinoids can release internal calcium stores in astrocytes and cause calcium waves (see
Figure 11.1
).

FIGURE 11.1 Calcium waves in mouse hippocampus astrocytes immediately after adding a short-acting molecule that stimulates the same receptors that respond to THC, the active ingredient in marijuana.

 

Reprinted from
Neuron
, Vol. 57, Navarrete, M. and Araque A. “Endocannabinoids Mediate Neuron-Astrocyte Communication,” p. 884, Copyright (2008), with permission from Elsevier.

This discovery indicates that the dreamlike state described by Baudelaire is indeed the result of marijuana causing calcium waves to ripple throughout astrocytes.

Alcohol and astrocytes have a longer history. When astrocytes are stained with antibodies to proteins related to cell structure, they show different morphology and reactivity in damaged brains. Studies have tried to determine how exactly alcohol causes brain damage by looking at astrocytes. The most intense study has only come about in the last 20 years. It seems that alcohol is able to affect calcium-binding proteins and cause calcium release from internal stores. The effects of alcohol also cause reactive oxygen species release, which can cause cell death.

Sadly, virtually nothing has been researched on astrocytes and hallucinogens such as mescaline, psilocybin, and LSD.

As pharmacology labs begin to focus on astrocytes, it will be interesting to see how the interactions of serotonin agonists, such as LSD and psilocybin, are related. The tryptamine structure of these molecules and others, such as AMT and DMT, shows they are related, but the circular thoughts and cool tones experienced with mushrooms is different from the infinity awareness and stark digitized experience of LSD.

The activation of cocaine is through the inhibition of dopamine reuptake. This is known to be an astrocyte-dependent process, but little work has been done on the astrocyte in relation to this activation and has mainly focused on neuronal circuits in reward centers of the brain. As with drugs, such as nicotine, cocaine, and so on, deep reward centers of the brain obviously play a major role, but the disregard of astrocytes in these centers, and cortical astrocytes in general, completely disrupts the understanding of human consciousness that could be achieved by studying the alterations that occur when unnatural substances bombard the brain and create such interesting and testable behavior.

The use of drugs can create dreamlike states and then affect our dreams as we withdraw. When his glial regeneration was likely stunted, Thomas de Quincey stated in
Confessions of an Opium-Eater
, “For this, and all other changes in my dreams, were accompanied by deep-seated anxiety and gloomy melancholy, such as are wholly incommunicable by words. I seemed every night to descend—not metaphorically, but literally to descend—into chasms and sunless abysses, depths below depths, from which it seemed hopeless that I could ever re-ascend. Nor did I, by waking, feel that I had re-ascended. This I do not dwell upon; because the state of gloom which attended these gorgeous spectacles, amounting at least to utter darkness, as of some suicidal despondency, cannot be approached by words.”

The withdrawal symptoms infecting our astrocytes and disrupting our basic dreams is a frightening prospect. Reading Baudelaire can reassure us when he describes the less aggressive hashish, “Let it be well understood then, by worldly and ignorant folk curious of acquaintance with exceptional joys, that they will find in hashish nothing miraculous, absolutely nothing but the natural in a superabundant degree. The brain and the organism upon which hashish operates will only give their ordinary and individual phenomena, magnified. Here is the drug before your eyes: a little green sweetmeat, about as big as a nut, with a strange smell.”

Our experiences reside in astrocytes. Drugs will influence and enhance them, but they are still acting on them, and they are us. When we are in a new situation and our calcium wave spreads to an area of cells responsible for a previous experience, we will have the feeling we have been here before—it’s a light disruption, putting us in a reflective trance. This feeling is astrocytes on the fringe of a previously felt experience being inundated.

We do know a bear avoids eating psychedelic mushrooms. Wolves avoid them as well. But do wolves experience déjàvu?

References
 

Agam, G., I.P. Everall, and R.H. Belmaker.
The Post-Mortem Brain in Psychiatric Research
. Norwell, MA: Kluwer Academic Publishers, 2002.

Baudelaire, C. Trans. A. Crowley.
The Poem of Hashish
, Whitefish, MT: Kessinger Publishing, 2004.

Cotter, D.R., C.M. Pariante, and I.P. Everall. “Glial Cell Abnormalities in Major Psychiatric Disorders: The Evidence and Implications.”
Brain Research Bulletin
, 55: 585–595, 2001.

de Quincey, T.
Confessions of an English Opium Eater.
Harmondsworth, UK: Penguin Books, 1995.

Domhoff, G.W.
The Scientific Study of Dreams
. Washington, DC: American Psychological Association, 2002.

Earleywine, M.
Mind-Altering Drugs
. New York: Oxford University Press, 2005.

Lancaster, F.E.
Alcohol and Glial Cells: Research Monograph 27
. Bethesda, MD: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 1994.

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