How to Think About the Brain, Part 2

The Dana Guide to Brain Health
by Floyd E. Bloom, M.D., M. Flint Beal, M.D., David J. Kupfer, M.D., The Dana Foundation

(Page 2 of 2)

Studying the Cells — The Bottom-Up Approach

We can also think about the brain in the opposite way, or "bottom up." This alternative approach involves starting with the brain's most basic components and then figuring out how they connect with each other.

The most basic working unit of the brain is a special type of cell, the neuron. You have approximately 100 billion neurons — as many trees as there are in the Amazon rain forest. But neurons are not the only cells in the brain: they are actually outnumbered ten to one by another type, glial cells. These cells maintain a healthy and nurturing microenvironment within our heads for the neurons to operate at their best.

So what do neurons actually do? Since the 1920s, neurologists have known that neurons generate minute electrical signals. Each neuron alive in your brain at this moment is producing a tiny voltage, a potential difference between the charge inside the cell and the charge outside. Under certain conditions, such as when a signal comes in from a neighboring cell, tiny channels open in the wall of the neuron so that there is a sudden, brief interchange of ions (atoms with an electrical charge, in particular sodium and potassium). This ion interchange causes a temporary shift in the neuron's charge — an electrical blip called an action potential. Action potentials last for only about one thousandth of a second. Yet a neuron will typically fire off a hundred or so every second. This traffic in charges represents the "moving parts" of the brain, the actions that make it work. Ultimately all that we are — all our memories, hopes, and feelings — can be boiled down to the banal transfer of a few ions across the membrane wall of our brain cells.

Using the right sensors, we can read those electrical signals through the bone of the skull; the result is the valuable diagnostic tool called the electroencephalogram (EEG; for more information, see chapter 2). Over the last few decades, furthermore, technology has enabled neurophysiologists to record the activity of a single neuron. Therefore, we have a fairly good idea of what makes those little building blocks of our brains work.

What happens once a neuron has generated an action potential? This tiny blip, some eighty thousandths of a volt in amplitude, buzzes away at speeds up to 250 miles per hour along the biological equivalent of a wire: an axon. But unlike any household electrical circuit, the brain isn't wired so that all neurons form one single continuous network. Instead, in most cases, there is a gap between the axon of one neuron and the next neuron. This gap is called a synapse. It is as impossible for the action potential to cross a synapse as it is for a car to screech down a road and then float across a river. This might seem to be a cumbersome weakness in our wiring, but it is actually a powerful advantage.

The brain has an alternative way to send a signal across the fluid-filled gap. When the electrical impulse invades the end of the axon, it triggers the release of a chemical that can spread across the synapse and activate the target neuron.

This chemical, because it transmits a signal, is known as a transmitter (or a "neurotransmitter," if we want to make absolutely clear that it is at work in the brain). Once the transmitter hits the target cell, it enters into a kind of molecular handshake with a custom-made protein, a receptor, on the outside of that cell. This molecular handshake then causes the opening of the tiny channels into that neuron so that ions can cross over, once again generating the electrical signal. The brain therefore is not like a computer or any other electrical device, because it operates by means of a cascade of alternating electrical and chemical events.

Furthermore, there are many different transmitters in the brain, each with several different subtypes of receptors. So unlike a standard electronic circuit within a computer, which can only be on or off, the brain has a powerful spectrum of functions. Different chemicals will trigger different states within the brain. To appreciate just how important chemical signaling is to brain function, and hence to our mental abilities, let's take a look at drugs.

All drugs that modify moods and feelings, whether prescribed or proscribed, do so by changing the availability or the efficacy of different transmitters within the brain. For example, some 30 years ago scientists discovered that the drug morphine worked by imitating a naturally occurring neurotransmitter called enkephalin (literally, "in the head"). But that does not mean that it is natural or safe to take the most abused derivative of morphine, heroin. Enkephalin is released in minute amounts as and when it's needed in the brain; then, even more important, it is disposed of very rapidly. Not so with heroin. First, it is not released in a small quantity exactly where it is needed; a heroin user effectively marinates his or her whole brain, setting the drug free to act wherever there are appropriate receptors. Second, when heroin does encounter a receptor and enters into a molecular handshake, the drug can't be removed as readily as its natural counterpart. Because heroin is a different chemical, it will remain stubbornly in place. The result is like a handshake with an excessively strong grip. And just as the hand being gripped quickly starts to turn numb, the brain's special receptors become less sensitive. The heroin user needs increasing amounts of the drug to obtain the same effect, one sign of an addiction (C29).

The powerful effects of drugs on the brain surely demonstrate the importance of transmitters and, above all, of the connections over which they operate. Even the awesome number of neurons in our brains is dwarfed by the number of connections between them. There can be as many as 10,000 inputs to any one neuron. One estimate has it that counting each connection in your cortex alone, one a second around the clock, would take you 32 million years!

Making Connections — The Dynamic Approach

Looking at the connections our brain cells forge is a sort of middle approach, halfway between studying large brain regions and examining single cells. It is this aspect of the brain that will most likely allow us to discover what it is about these squishy organs that makes humans such an intelligent species, and makes each one of us unique.

As you'll see in more detail in Part II of this book, we are born with pretty much all the neurons we will ever have. (In fact, many brain cells die off during childhood.) But the marvelous feature of being human is that many of the connections among those neurons are laid down after we are born. This forging of connections in the most basic and broadest sense underpins what we refer to as learning. We have highly adaptable brains that reflect and benefit from our experiences. In contrast, simpler organisms like bugs operate at the dictates of their genes, following preprogrammed instincts.

We call the adaptability of our human brains plasticity. Our brains reflect each new experience. As a consequence, we become individuals. Everyone undergoes different experiences, and everyone's brain develops differently. Of course genes play an important part in constructing the molecular machinery at work on each side of your synapses. But there are about 1 billion more connections in your brain than genes in your chromosomes; it is impossible for each connection to be programmed by a gene. Instead, the connections are shaped by your experiences.

The basis of this adaptability is the growth of connections between cells, strengthened and promoted by the activation of the relevant neurons. An axon coming from one neuron makes contact with the next neuron along the circuit by means of what are called dendrites on the receiving neuron. The more dendrites a neuron has, the more connections it will be able to make and the greater the circuitry underpinning a particular process or function. Just as a muscle grows with appropriate exercise, so selective circuits in the brain branch out and expand as they are worked. We can see this change even at the level of a single neuron. In one study with adult rats, half were housed in humane but isolated cages while the other half were housed collectively and exposed to interactive objects, such as ladders. The neurons from the group in the temporarily "enriched" environment showed more dendrites emanating from a single cell than those in the nonenriched group.

The more sophisticated a species, the longer it takes for an individual to grow to adulthood. We humans are the most sophisticated animals of all, so we take many years to develop. Our brains need that much time to collect and store the experiences that shape our minds. Childhood is usually a time of exploration, of making the mental connections that go along with the growing connections among our brain cells. That is why an individual's circumstances in youth help mold that person's personality, skills, and other qualities. (For more on brain development in childhood and adolescence, see chapters 6 and 7.)

But learning doesn't have to stop in childhood. The plasticity of our brains means that they can usually adapt to further challenges. A recent study showed that London taxi drivers, who have to memorize all the street names and routes of that huge city, have a larger part of the brain relating to memory than do other adults of a similar age. Another striking example of our brain's ability to learn entails not a lifetime at a profession but merely five days spent practicing a piano exercise — this study showed that over such a short time the brain territory allocated to the fingers became enhanced. Even more amazing, mere mental practice has a similar effect on the brain.

But is the brain's power to learn limited as we get older? We have already briefly explored the physical basis of "blowing the mind" with drugs. Sadly, old age can bring the horror of "losing one's mind" because of degenerative diseases like Alzheimer's (C67). In this disorder, still not fully understood, the connections that a person's brain has so painstakingly accumulated throughout life gradually become dismantled: increasingly, everything around the person comes to "mean" less. Imaging techniques have now revealed that certain brain regions in Alzheimer's patients shrink far faster than in healthy individuals of a similar age. This finding has an encouraging implication: the symptoms of senile dementia that come with this disease are not a natural consequence of aging but are due to some special factor or factors that are as yet a matter of conjecture.

In fact, healthy older brains retain their plasticity. We can see this in the often remarkable recoveries of people who have had strokes (C59, C60). Parts of their brains suffered severe damage, having been deprived of blood and oxygen for significant periods. Nevertheless, many of these people are able to offset the damage and regain functions they initially lost. Their brains create new neural pathways, or start to use old ones, to bypass the damaged areas. Once again, the brain responds to experience by creating new connections and new functionality. (For more about the brains of older adults, see chapter 8.) In the near future the brain sciences will be shedding more light on these mechanisms of plasticity, as well as giving us insight into the specific losses that characterize Alzheimer's disease and other disorders.

Because of plasticity, as we go through life, our brains become increasingly personalized. Everything we encounter will be interpreted in the light of all that we have seen before. It is this personalization of the brain that gives rise to the mind. Viewed in this way, the mind is not some airy, whimsical alternative to the physical brain, but the aspect of it that makes each of us unique.

The Director of the Royal Institution of Great Britain, Dr. Susan Greenfield, has a memory that captures nicely the mystique of the physical human brain and its relationship to mind. Here is how she tells it:

"Once upon a time, over 25 years ago, I was undertaking a dissection of the human brain as part of a college class. Each pair of us students had our own plastic bucket, containing in preservative liquid the organ that had once defined a unique person. I stared down at this odd object in my fingers, resembling two compacted giant walnuts with a smaller walnut on the back. A macabre thought struck me: What if I weren't wearing protective gloves and got a piece of this brain stuff stuck under my fingernail? Would that be a thought or a memory, a habit or a feeling? Exactly what part of the individual would be nestling on top of my finger?"

Evocative, fundamental questions remain to tantalize. We are at an exciting time, when we no longer need to think about the brain as a collection of static anatomical regions, nor as a mere mass of generic cells and chemicals. We can now peek into the brain and see it shaping and reshaping every moment of our lives. It is truly the most dynamic and the most personal part of our bodies.

Copyright © 2003 by The Charles A. Dana Foundation

About the Author

is Chairman of the Department of Neuropharmacology at The Scripps Research Institute in California, President of the American Association for the Advancement of Science (AAAS), and former editor in chief of the journal Science. He lives in San Diego.

M. Flint Beal, M.D., is Neurologist in Chief of the New York and Presbyterian hospital, and Anne Parrish Titzell Professor and Chairman of Neurology at the Weill Medical Collage of Cornell University. He lives in New York City.

David J. Kupfer, M.D., is Thomas Detre Professor and Chairman of the Department of Psychiatry at the University of Pittsburgh School of Medicine, and Director at the Western Psychiatric Institute and Clinic there. He lives in Pittsburgh.

The Dana Foundation is a private philanthropic organization dedicated to furthering advances in science, health, and education. The Dana Press, which directed the Dana Guide to Brain Health, is the Foundation's publishing division.