Massive Cell Death, Part 2

A User's Guide to the Brain: Perception, Attention, and the Four Theaters of the Brain
by John J. Ratey, M.D.

(Page 5 of 12)

During their journey, the neurons are fed and guided by caretaker glial cells, which form a scaffolding along which the neurons migrate-a lattice of support, guidance, protection, and nourishment. After the neurons reach their final places, the glial cells remain, although they change their shape and molecular properties in order to perform different functions. Two types of glia appear: one type controls the metabolism and function of the neurons; the other, which coats the axons with a fatty substance called myelin, controls how fast axons conduct information. The two main types of cells, neurons and glia, make up the brain, which is pretty much complete by the eighth month of pregnancy. At this point there are twice as many neurons as in the adult brain. As the brain ages, neurons that are weak or unused or simply don't fit the job that needs to be done are pruned away, to leave more efficient connections for those that are performing brain work. The principle of "Use it or lose it" begins, with nonworking, "couch-potato" cells dying off while those that are exercised get stronger and develop more connections.

Millions of the neurons travel amazing distances, the equivalent of a hike from New York City to San Francisco. Where they settle helps determine our individual temperament, talents, foibles, and quirks as well as the quality of our thinking processes. If neurons lose their way on their long journeys, developmental disorders may result, which is why it is so important that a pregnant woman not ingest harmful substances; a particular chemical in the brain at a critical moment will send neurons down the wrong fork in the road, or simply stop the process and cause havoc. Alcohol, nicotine, drugs and toxins, infections such as German measles, and lack of certain nutrients such as folic acid can interrupt the migration.

Once neurons have settled in at their final home-why they stop where they do is still a mystery-they grow dendrites and axons to communicate with other dendrites and axons. The tentacles reach for each other but don't quite touch. Like the outstretched fingers of God and Adam on the ceiling of the Sistine Chapel, they remain separated by a small gap, called a synaptic cleft. The axons and dendrites communicate by sending chemical messengers-neurotransmitters-back and forth across the synapse. A single neuron may be communicating across 100,000 synapses.

Chemical signals, called trophic factors, tell the axons where and how to connect. Whether or not electrical stimulation becomes sustained determines whether a connection between neurons survives or even whether a given neuron lives or dies. Because of the huge overproduction of neurons, there is not enough biochemical juice to support all of the axons searching for connections. Axons battle for limited sites, and those that lose the competition perish. Others that try to connect with the wrong kind of neuron are cut off from nourishment. However, there is no mindless competition of neurons for survival. Instead, forces external to each element in question (receptor, synapse, etc.) determine its degree of use and hence its survival. At first the activity that determines survival is random and spontaneous, but it becomes more organized as the fetus, and then the baby, receives input from its environment.

Two sequential pruning processes then fine-tune the initial neuronal networks that are formed. One causes the loss of entire neurons and the other the loss of branches and synapses. Both seem to involve competition for limited amounts of specific chemical signals released by the target cells. In the first process, neurons that fail to get enough signals from their target cells undergo cell death. This eliminates neurons that have made inappropriate connections and helps match the number of neurons to the number of target cells. In the second process, the connections between surviving neurons are refined by the removal of some dendrites and their synapses and the stabilization of others in a process that depends on electrical activity along the axons and competition among neighboring target cells. As the brain matures, the synaptic connections are further modified by use.

A period of cell death during the later stages of pregnancy wipes out almost half the neurons in the brain, which are probably phagocytized, or eaten up, by the support cells of the brain and the molecules recycled locally. There is a drop from about 200 billion neurons to 100 billion. This widespread cell death is normal, for it eliminates the wrong and weak connections that could inhibit efficient and proper brain function. This is a classic example of the incredible resourcefulness of evolution, which makes us highly adaptable creatures. It also points to the fact that even at the very beginning of development the brain is a social organ: where there is no connection, there is no life.

When a baby is born, it has millions of good connections waiting for a specific assignment. As the world makes demands, many of the connections are enlisted for specific jobs: seeing, babbling, remembering, throwing a ball. Connections that aren't used are eventually pruned. In the absence of the proper stimulation, a brain cell will die, but offer it a diet of enriched experiences and its neural synapses sprout new branches and connections.

Neurons that survive communicate rapid-fire across the synapses. The more firing that occurs across a specific connection, the stronger that pathway becomes. Billions of these exchanges take place continuously throughout the brain. Some connections transmit and receive signals often, others only occasionally, and the messages change constantly. The exact web of connections among neurons at a particular moment is determined by a combination of genetic makeup, environment, the sum of experiences we've imposed on our brains, and the activity we are bombarding it with now and each second into the future. What we do moment to moment greatly influences how the web continually reweaves itself.

Excerpted from A User's Guide to the Brain by John J. Ratey, M.D. Copyright © 2002 by John J. Ratey, M.D.. Excerpted by permission of Vintage, a division of Random House, Inc. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.

About the Author

John J. Ratey, M.D., is an associate professor of psychiatry at Harvard Medical School. He has lectured extensively and published many articles on the topic of treating adults with ADD. Dr. Ratey is the author of A User's Guide to the Brain and the co-author of Driven to Distraction. He lives in Cambridge, Massachusetts, where he has a private practice.