DO ALL PARTS OF THE BRAIN LEARN?

DO ALL PARTS OF THE BRAIN LEARN?

The processes that we just described do not happen in just one part of the brain. There are indeed specialized neural networks, especially in a part of the brain called the hippocampus, where learning occurs and memo­ries are created. (People who have had damage to this part of the brain cannot learn new things, although they can remember things that happened before.) However, most forms of plasticity can occur all over the brain and affect all brain function.

For us to be able to function normally, all brain processes need to pro­ceed unimpaired. All of the neurotransmitter systems need to be working.

The brain needs to change with time to reflect previous experience—that is, learn—to restore balance if it is over- or understimulated.

THE DEVELOPING BRAIN

While the brains of adults change all the time, what goes on in adults is trivial compared to the phenomenal changes that occur while the brain is developing. The brain assembles itself carefully through the process of neurons growing out, and through chemical signals around them, gradu­ally finding their way to the correct destination, where they make the connections that they then maintain. During this time of life, the physi­cal changes in the brain are dramatic. New synaptic connections are being made at a high rate every day. The growing brain also has its own way of "forgetting." Many of the neurons growing out never reach their destination and die in the process. Others reshape their connections until they are correct. Through all of this furious growth, neurons must remain active or they can fail to make their appropriate connections. Therefore, changes in neuronal function that in an adult would simply shut down a pathway for a while, in a developing brain can have more drastic consequences.

Growing neurons are affected by processes that don't affect the neurons of adult brains. Exposure to substances that inhibit cell growth has some impact on an adult brain but a devastating impact on the developing brain. The neurotoxic element mercury provides a good example. Mer­cury affects the function of the adult brain and can lead to serious, but largely reversible, disruption of brain function. However, exposure of the brain of the developing fetus to mercury disrupts brain development so totally that severe mental retardation results. For example, an industrial spill of mercury into the water near a small, coastal Japanese town called Minamata contaminated the fish that were the local food source. While many adults experienced diseases that eventually resolved, many children born during this time frame had terrible disruption of normal brain development and remained mentally retarded throughout their lives.

Recently, medical imaging techniques have made it possible to study the development of the human brain at various points from birth to adulthood. Some of the most interesting studies use magnetic resonance imaging (MRI) with the machine set to reveal the white matter of the brain, the myelin insulation on the nerve cell axons. As the brain matures, the connections between cells become permanent, and then they are insulated with myelin. So, imaging for the myelin tells the scientist just how much development has occurred in a brain area. The big news is that the human brain is not fully developed until late in adolescence. And among the last parts to develop are the frontal lobe areas that give us the capability of inhibiting inappropriate behavior, handling complex tasks, and planning ahead. When we lecture about this, we often make the point that from the standpoint of the brain, adolescents are not "young adults," but rather, "big kids,"

We believe it is very important to teach kids that their brains are still developing through adolescence. This means that they have the opportu‑  when we were drunk (see the "Alcohol" chapter for more information). presses maze learning. So, now we may know why we forget what we did are also suppressed in humans.

injury. There is every reason to believe that learning and neuroplasticity and the CNS does not reorganize its neuronal connections following glutamate cannot bind there, LIP does not occur, rats do not learn mazes, oratory experiments, if we chemically block the NMDA receptor so that how memory occurs and how some drugs disrupt it. For example, in lab-learning and other forms of neuroplasticity. It may teach us much about receptor, because it appears to be one of the most important receptors for strengthening that synapse.

the NMDA receptor is activated, the cell "remembers" the signal by receptor is like a memory switch. When the cell is receiving a signal and The calcium causes LTP to occur at those synapses. Thus, the NMDA Many drugs affect the ability of the brain to learn—there is no question only when the cell is receiving excitatory signals through other synapses. receptor, has the very special property of letting calcium into the cell mate. This particular subtype, the NMDA (the N-methyl-D-aspartate) Alcohol in rats blocks NMDA receptors, suppresses LTP, and sup 

presses blocks a certain subtype of the excitatory neurotransmitter gluta¬manifestations about it. But which drugs have which effects, and for how long? One of the best stories about the effects of drugs on learning was told to one of us by a drug company representative during an airplane trip. It seems that some of the professional staff from his company were making a quick trip over­seas to a meeting, and they needed to sleep during the plane ride because their lectures were scheduled almost as soon as they were to arrive. So, this group had a few alcoholic drinks and then took one of their newly marketed sedatives (a benzodiazepine) to get to sleep. Everything went well, including the lectures, and the scientists returned home in a couple of days. The only problem was that when they returned, they remembered nothing of the meeting—not their lectures or those of anyone else. They

did not know that the drug they chose, in the dose they chose, would have

powerful amnesiac effects, especially when mixed with alcohol. This story is legend in the pharmaceutical industry, and whether it is exactly true does not make any difference. It illustrates the point that even the people who develop and manufacture drugs by the highest standards may not know every effect they can have and how long these effects can last.

There are basically three ways in which drugs can affect learning: they can impair the ability of the brain to store information (amnesia), they' can distort reality, or in some cases, they can stimulate the brain to

increase learning.

By far the most common effect of drugs is to suppress learning. Almost

all of the drugs that have sedative or anxiety-reducing properties impair the retention of information. Although we do not know exactly how this happens, there are three mechanisms that have been proposed at the syn‑

aptic level.

The first of these is increased inhibition. We know that many sedative drugs increase GABA-mediated synaptic activity, which inhibits the fir­ing of neurons. The experimental data suggest that this increase in inhibi­tion can reduce the effects of the type of neuronal firing that is usually necessary for LTP, and thus prevent neuroplasticity.

The second of these mechanisms is reduced excitation. Some drugs, such as alcohol, not only increase GABA function (and thus inhibition) but also suppress the glutamate-mediated excitatory channels (the NNIDA receptor channels) that let calcium ions into the neurons. This reduction in calcium entry prevents the signaling mechanisms within the neurons that lead to long-term synaptic changes.

Finally, there are drugs, such as the THC in marijuana, that act through their own receptors to change cell biochemistry so that learning is   impaired. From what we know of their biochemistry, they may directly

regulate the signal-processing pathways within the cell that govern the strength of synaptic activity, perhaps by suppressing the signals thatmediate LTP or, alternatively, by enhancing the processes underlying LTD and/or depotentiation.

Now that we know about LTD and depotentiation, it is easy to imagine that there would be reasons for the CNS to reduce activity in some path‑

ways and thus "forget" some neuroplastic changes. Therefore, it is com‑

pletely reasonable that some drugs could enhance this type of signaling, reducing the ability to learn.

On a brighter note, neurobiologists are exploring ways to use drug therapy to enhance learning. This research is particularly important for the many people who suffer from Alzheimer's disease or other brain dis­orders that impair learning. Most of the rest of us would also relish the

ability to learn more or faster. There are some tantalizing clues that this may be possible.

One of the most interesting clues comes from an experience that almost all of us have had. It's the "Do you remember what you were

doing when ... ?" question. Every generation has at least one of these ques‑

tions. For older people, it's what they were doing when they heard that JFK

was assassinated. Nearly everyone recalls the fateful morning of 9/11. Think

of an example: the first time you had a very important and emotional expe­rience, either positive or negative.

Why is it that we remember some experiences so well, and not only the event but maybe what clothes we wore, what the room looked like, what we ate? Ongoing experiments shed a lot of light on this phenomenon. Dr. James McGaugh (of the University of California at Irvine) took two similar groups of people and placed them in separate but similar rooms with all sorts of cues, or decorations. The goal was to subject the groups to an

emotional story and to see how well they remembered the story and the environment (the room) in which they experienced the event.

What makes this experiment interesting is that one group was given a drug (propranolol) that blocks a particular subtype of adrenaline recep‑

tor—the beta-adrenaline receptor. This receptor is the one responsible for the increase in heart rate and blood pressure that occurs under physical or emotional stress; the blocker, propranolol, is used to control blood pressure and heart problems in some patients. So, one group was com‑

pletely normal, while the other group had their excitatory adrenaline activity blocked.  The experimental subjects were then told a heartbreaking story about an injured child. After a period of time the two groups were removed from their rooms and then asked to recall the story and the details of their environment in the room. Both groups remembered the story. How­ever, only the normal (undrugged) group remembered the details of the room. The treated group remembered very little of their environment.

What does this teach us? We all know that we tend to learn what inter­ests us, and we know that we remember emotional events. Now we know why. The adrenergic system apparently delivers signals to the brain that facilitate learning and remembering the environment associated with an emotionally powerful event. This is probably a very important character­istic for both humans and other animals to have, because it tends to help us remember events and places that were either wonderful or threatening, and thus adjust our future behavior accordingly. So, now it is clear why a smell or a face or a place might make you feel good or bad, even if you cannot immediately recall why: your brain is recalling an emotional

experience.

This insight into learning is useful in several ways. First, it illustrates how important it is to be alert and interested in what we are trying to learn. When we are sleepy or depressed we are poor learners, in part because our adrenergic system is not activated. To really learn or teach something, we must include an emotional component.

In addition, this experiment suggests that there may be ways to facili­tate learning through manipulating brain chemistry. Neuroscientists already know that the adrenergic system is not the only modulator of learning. However, increasing the function of any of these systems has proven difficult to achieve without producing unacceptable side effects.

At this point, no drug has yet been approved to increase learning. Until then, readers, you'll have to "trick" your brain by studying what is excit­ing and by getting excited about what you must study!