The Root of Thought (11 page)

Before we are born, a neuronal framework like the branches of the blueberry bush is established. Then astrocyte growth snowballs at birth. Unfortunately, neuronal studies have dominated.

We can gather some evidence from neuronal-focused research into how astrocytes grow and develop in the womb at birth and early childhood. With neuronal tendrils sinewing out of the grey glial goo, transmitting rapid signals at the beck of our pondering, contemplating and understanding astrocytes, the pre- and post-natal development of the primate brain are established when we are born. Neurons are used by beings to acquire rapid information about their environment through their limited senses. Only with our regulatory muscle—our astrocytes—can we reach beyond our limitations by considering the sensory information. Only through our glia can we reach a higher understanding of our existence.

The cortex is where higher thought is processed in our astrocytes. Although most research has been neuronally focused, in the last 30–40 years, a better understanding of the nature of our cortical development has been taking shape. One of the first scientists to tackle the method of cortical development was none other than our old friend Cajal. Cajal speculated as to the nature of connectivity in the cortex while, as usual, assuming the neuron held the greatest importance.

When the brain develops before birth, cells called radial glial stretch out from the ventricular fluid. The ventricles sit inside our brain like a pond in spring and summer. All growth and activity surrounds the pond. Like the growth of tadpoles becoming frogs, ventricular pools of fluid influence cell division. Cells divide next to the pools and expand out to form the brain in an inside-out manner. Cells dividing from radial glia can become any cell type in the brain. Neurons are formed first and set down like the streets of a housing development.

Much of our wealth of knowledge into brain cell development comes from Pasko Rakic and his wife Patricia Goldman (1937–2003), both developmental neurobiologists at Yale University. Rakic started his career in the former Yugoslavia in the Soviet eastern bloc. Injecting monkeys with radioactive material in the 1960s, Rakic was able to follow cell morphology and lineage in the primate brain during development.

Prenatally, radial glial cells extend long distances from the center of the brain to the outside surface. If you think of the ventricle pools as the body of a porcupine, the radial glia are its quills. Radial glial cells appear around gestation week seven as the part of the embryo’s brain sprouts and grows. Shortly after radial glia appear, they begin dividing at the ventricle. The cycle of cell division starts with the radial glial cell body migrating up its long and thin processes that stick up from the ventricle; the porcupine quill reach up like a blind man’s cane to test its environment. This phenomena is demonstrated in
Figure 7.1
. As the cell decides to divide, it begins to replicate its DNA as it migrates down the porcupine quill back to the ventricle. It then becomes two cells, one of which migrates back up its long radial glial cell mother and becomes a neuron.

FIGURE 7.1 A neuron climbing like a squirrel up its radial glia mother tree

Reprinted from Brain Research Reviews, Vol. 55, Issue 2, Rakic, P., “The Radial Edifice of Cortical Architecture: from Neuronal Silhouettes to Genetic Engineering,” p. 208, Copyright (2007) with permission from Elsevier.

The radial glial cell is also a mother in the sense that it guides its progeny to their places in the world. In this case, the world is our brain. After each new cell migrates up the radial glia to its new position in space, it morphs into a neuron. When mapping the cortex in the late nineteenth century, Cajal did so based on connections neurons make when bringing information from the sensory and sending to the motor environments. Based on neuronal connectivity, the cortical layers are numbered 1–6. Layer 1 is closer to the outside surface of the brain; layer 6 is deeper inside the brain.

Layer 6 forms first in development. Radial glial extend short processes near the ventricle, and bulbs of cells are laid down like seeds. At this point, as the fetus is bathed in embryonic fluid, the ventricular fluid takes up almost the entire space of the peanut-sized brain.

For the next 100 days, radial glia extend further out of the brain. They push through already established layers, through its continual neuronal offspring to what will be the outside of the brain. After the last layer is formed (layer 1, which is at the extreme outside of the brain), the neuronal support infrastructure of the cortex has been laid down like a map. In the second month of pregnancy, at the peak of proliferation, it is estimated that 200,000 neurons bud every minute.

The explosion of cell proliferation in primates compared to other animals is believed to be the reason for our unique folds of the cortical surface when we observe a brain removed from its skull. In a rat, the cortex has no folds and is simply an outer sheath covering the basal areas of the brain. However, in humans, the cortex folds and refolds to fit all the cell bodies in the cortex. It can be compared to shoving a crumpled blanket in a box that is too small. It won’t fit if you lay it flat, but if you fold it up or mash it in the box, it fits nicely. Because of our unique brain structure, the massive amount of cells in the cortex is one of the reasons the cortex is believed to be where higher thought is processed.

The cortex of the human is only about twice as thick as the rodent. Most mammal brains have long white tracks of axons from neurons extending out of or in to the cortex from our sensory and motor functions. However, if you flattened out all the folds and spread out the cortex like a cookie sheet, the human cortex would take up about 400–500 times more area than a rodent cortex. Of course, this isn’t as impressive when one considers the size of an elephant brain. Complex cortical folds exist in whales, elephants, and dolphins. For all we know, an elephant might have finally solved many of the problems of quantum theory. Although the cortical area from an elephant brain would probably take up more area, the human brain has a significantly higher glia-neuron ratio in the cortex.

After the neurons are put in their proper places, the last trimester of pregnancy is spent making neuronal connections in the brain. When the neuron reaches its niche after climbing like a caterpillar up the radial glial tree, it extends out growth cones. Like the head of a snake, the growth cone explores its environment for the best place to make a connection. Usually this is when it encounters another neuronal process. Both the axons and dendrites of neurons extend through growth cones. They have little hair-like structures on the end that help them move through the environment. The shaft of their extensions from the neuronal cell body extend incrementally as they reach out.

When they contact the next neuron, they form a connection and begin laying out the groundwork for the transmitters and receptors they use to communicate with one another.

The initial transmitter expression in the womb is a calcium-dependent process. Early in the embryonic stage, spontaneous calcium-dependent
electrical changes in neurons cause the transmitter to be expressed that will be used in the future by the neuron. If the calcium levels are tweaked, different types of transmitters can be expressed in the cells. This curious regulatory control by a calcium pulse draws parallels to the calcium wave of astrocytes as the control of information processing in the cortex.

While this occurs, areas near the ventricles begin dividing interneurons and oligodendrocytes. These cells provide functions to maintain the previously developed neuron—the interneurons inhibit other neurons and oligodenrocytes wrap fatty tissue around axons so they can better conduct electricity.

At this stage, deep brain structures nominally understood to be the seat of unconscious activity are formed. The limbic system and the basal ganglia become solidified. The basal ganglia are responsible for motor neuronal efficiency and are disrupted in Parkinson’s disease. The limbic system deals with our basic subconscious desires such as food and sex. Both are covered by the cortex, like a baby in a folded blanket.

After the neuronal framework is established, avenues and highways traversing the bulb behind our eyes, mouth, nose, and between our ears, extending to our limbs through our tail-like spine, are ready to be populated with our mind. Astrocytes begin to grow and fill niches near their support neurons, in places where they have easy access to sensory information to influence their calcium wave, places to experience the beauty of life, think about it, and transmit ideas into action through long-distance, quick communication down neuronal lines. Astrocytes are our mind. As they are about to peak, we slip out into the world, fully equipped to experience life as a human being.

Astrocyte proliferation coincides with birth. In rodents, which have a gestation period of three weeks, the peak of neuronal formation occurs at two weeks during the embryonic stage. Then astrocytes peak at birth or two days postnatally. A second wave of oligodendrocytes peak after birth. In humans, the timeframe follows the same course. As we are born, astrocytes become the houses next to the neuronal roads.

After the astrocyte explosion at birth, radial glia also stop dividing and turn into astrocytes themselves. Their long processes, now extending to the outer regions of a fully layered cortex, shrink back to the ventricles and assume an astrocytic morphology, like a man on stilts coming down
to the ground and taking off his clown makeup. There astrocytes reside next to the ventricles as we enter adulthood. They are able to divide and create new cells throughout our lifespan.

Astrocytes are the basis for life in the brain. They self-replicate, are promiscuous, spit out progeny, and give us the ability to attempt to make sense of our world.

After the astrocytes have been placed next to their neuronal roads, synaptogenesis occurs. Synaptic connections have already been made. However, for proper communication, the strengthening of synapses through bulbs sprouting off the axons and dendrites, like flower buds, need to be formed. Neuronal connections are meaningless without astrocytes there to tell them what to do. This astrocyte influence over synaptogenesis sadly has not been adequately studied. However, the obvious implications that it does not occur until astrocytes are present means that astrocytes communicate this effect. Interestingly, evidence in the last 15 years has pointed to a reduction in synaptogenesis in Down’s syndrome. However, the role of astrocytes in reduced synaptogenesis in this disorder has never been studied.

The extreme growth of the brain around birth and immediately afterward is when the skull enlarges. The weight of the human brain more than doubles in size from birth to age 1. Much of this is due to astrocyte proliferation.

Apoptosis is a prevalent phenomenon involved in development—it is the term to describe the killing of useless cells. Excessive neurons are created during development. As the brain grows after birth, an incredible amount of synaptic connections are also made. However, in a twisted mass genocide, other cells send signals that eliminate the excessive cells to make room for their own. The cells are ultimately scavenged away. How the elimination of synapses occurs is largely unknown. However, it might be possible that astrocytes cause the extensive generation of the synapses and then decide which ones are necessary and which ones are expendable, like a medieval king choosing his harem.

From gestation week 29 until birth, our brain grows by 160 percent. When we are born, our brain is 25 percent of the adult volume. By the time we are 6 years old, our brain reaches 90 percent of the size it will be when we are an adult.

The long neuronal axons, which constitute the white matter regions of the brain, increase in volume systematically after birth. After
oligodenrocyte differentiation, throughout childhood, they begin to actively wrap fatty tissue around neurons. The graded increase in brain size is likely due to white matter size increases and fatty tissue around axons. It is known that astrocytes can communicate to oligodendrocytes, and some aspects of the intense insulation of axons might be controlled by astrocytes.

Although the brain increases in size overall throughout our childhood development, more interestingly is how the cortex increases and decreases in size. After birth, development of the cortex increases until about age eight. At this time, the brain begins to become systematically streamlined. The volume of the cortex is much smaller in adults than in eight year olds. At about age four, we begin to experience memories and dreams, after glia arrive and establish themselves postnatally. If neurons were responsible, wouldn’t we have memories of the third trimester?

Interestingly, different areas of the cortex have different ages for the peak in their volumes. It was shown that from preschool until ages six to nine, a 13 percent increase in the volume of the cortical grey matter occurs. This then declines by 5 percent into adulthood. Frontal lobe areas reach their peak volumes at age 12. Parietal lobes reach their peak volume at about 11 years of age. Temporal regions reach their peak volumes at about 16 years. Occipital regions where visual integration occurs show a continuing linear increase into adulthood.