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How the Mind Works: Revelations

Jean-Pierre Changeux is France’s most famous neuroscientist. Though less well known in the United States, he has directed a famous laboratory at the Pasteur Institute for more than thirty years, taught as a professor at the Collège de France, and written a number of works exploring “the neurobiology of meaning.” Aside from his own books, Changeux has published two wide-ranging dialogues about mind and matter, one with the mathematician Alain Connes and the other with the late French philosopher Paul Ricoeur.

Changeux came of age at a fortunate time. Born in 1936, he began his studies when the advent both of the DNA age and of high-resolution images of the brain heralded a series of impressive breakthroughs. Changeux took part in one such advance in 1965 when, together with Jacques Monod and Jeffries Wyman, he established an important model of protein interactions in bacteria, which, when applied to the brain, became crucial for understanding the behavior of neurons. Since that time, Changeux has written a number of books exploring the functions of the brain.

The brain is of course tremendously complex: a bundle of some hundred billion neurons, or nerve cells, each sharing as many as ten thousand connections with other neurons. But at its most fundamental level, the neuron, the brain’s structure is not difficult to grasp. A large crown of little branches, known as “dendrites,” extends above the body of the cell and receives signals from other neurons, while a long trunk or “axon,” which conducts neural messages, projects below, occasionally shooting off to connect with other neurons. The structure of the neuron naturally lends itself to comparison with the branches, trunk, and roots of a tree, and indeed the technical term for the growth of dendrites is “arborization.” (See the illustration below.)

The Neuron & the Synapse

We’ve known since the early nineteenth century that neurons use electricity to send signals through the body. But a remarkable experiment by Hermann von Hermholtz in 1859 showed that the nervous system, rather than telegraphing messages between muscles and brain, functions far slower than copper wires. As Changeux writes,

Everyday experience leads us to suppose that thoughts pass through the mind with a rapidity that defies the laws of physics. It comes as a stunning surprise to discover that almost the exact opposite is true: the brain is slow—very slow— by comparison with the fundamental forces of the physical world.

Further research by the great Spanish anatomist Santiago Ramon y Cajal suggested why the telegraph analogy failed to hold: most neurons, instead of tying their ends together like spliced wires, leave a gap between the terminus of the neuron, which transmits signals, and the receptor of those signals in the adjacent neuron. How signals from neurons manage to cross this gap, later renamed the synaptic cleft (“synapse” deriving from the Greek for “to bind together”), became the major neurophysiological question of the early twentieth century.

Most leading biologists at that time assumed that neurons would use the electricity in the nervous system to send signals across the cleft. The average synaptic cleft is extremely small—a mere twenty nanometers wide—and though the nervous system may not function at telegraphic speed, it was not difficult to imagine electrical pulses jumping the distance. Further, given the speed with which nerves react, the alternative theory, that electrical pulses would cause a chemical signal to move across the cleft, seemed to rely on far too slow a mechanism. But as the decades passed, hard evidence slowly accumulated in support of the chemical theory. According to Changeux, experiments began to suggest that “the human brain therefore does not make optimal use of the resources of the physical world; it makes do instead with components inherited from simpler organisms…that have survived over the course of biological evolution.”

A remarkable experiment by Otto Loewi in the 1920s first suggested how the brain makes use of its evolutionary inheritance in order to communicate. Loewi bathed a frog’s heart in saline solution and stimulated the nerve that normally slows the heartbeat. If the slowing of the heart was caused by a chemical agent rather than an electrical impulse, Loewi reasoned, then the transmitting chemical would disperse throughout the solution. Loewi tested his hypothesis by placing a second heart in the solution. If nerve transmission was chemical rather than electrical, he supposed, then the chemical slowing down the first heart, dispersed throughout the solution, would likewise slow down the second heart. This is exactly what happened. Loewi named the substance released by the relevant nerve, called the vagus nerve, Vagusstoff; today it is known as the neurotransmitter acetylcholine. By the 1950s, further experiments had definitively proved that most neurons, while using electricity internally, must resort to chemicals to cross the synaptic cleft and communicate with the next neuron in the chain.

Changeux began his work at this stage, when the basic methods for neuron communication had been determined but the detailed chemical mechanisms were just opening up to research. Thanks to new high-resolution images from electron microscopes, first taken by Sanford Palay and George Palade in 1955, biologists could finally see the minute structures of the synapse. They discovered that the transmitting end of the neuron, called the nerve terminal, comes packed with tiny sacs, or vesicles, each containing around five thousand molecules of a specialized chemical, the neurotransmitter. When an electrical signal moves down the neuron, it triggers the vesicles and floods the synaptic cleft with neurotransmitter molecules. These chemical neurotransmitters then attach to the proteins called receptors on the surface of the neuron that is located just across the synaptic cleft, opening a pore and allowing the electrically charged atoms called ions to flow into the neuron. Thus, the chemical signal is converted back into an electrical signal, and the message is passed down the line.

These processes were still somewhat mysterious in 1965, when the young Changeux, working with his teacher Jacques Monod and the American scientist Jeffries Wyman, produced one of the theories for which he became best known. The three scientists, then studying metabolism, attempted to explain how the structure of an enzyme could stabilize when another molecule attached to it. Changeux later saw a parallel with the nervous system. When a chemical neurotransmitter binds to a receptor it holds the ion pore open, ensuring its continuing function, a critical step in converting the neurotransmitter’s chemical signal back into an electrical pulse. Changeux’s discovery established the groundwork for the way many neurons communicate, and his findings were based on the more general paper he had coauthored with Wyman and Monod.

With a working theory for neuron communication established, Changeux then turned to the ways that larger structures in the brain might change these basic interactions. A longstanding theory, introduced by Donald Hebb in 1949, proposed that neurons could increase the strength of their connection through repeated signals. According to a slogan describing the theory, “neurons that fire together, wire together.” Repeated neuron firings, Hebb believed, would produce stronger memories, or faster thought patterns. But researchers found that certain regulatory networks could achieve far more widespread effects by distributing specialized neurotransmitters, such as dopamine and acetylcholine, throughout entire sections of the brain, reinforcing connections without the repeated firings required by Hebb.

Changeux focused on these specialized distribution networks. It was long known that nicotine acts on the same receptor as the neurotransmitter acetylcholine. Changeux recognized that this could explain both nicotine’s obvious benefits—greater concentration, relaxation, etc.—as well as the drug’s more puzzling long-term effects. For instance, while cigarettes are dangerous to health, some studies show that smokers tend to suffer at significantly lower rates from Alzheimer’s disease and Parkinson’s disease. Changeux found that nicotine, by attaching to the same receptors as acetylcholine, reproduces some of the benefits of acetylcholine by reinforcing neuronal connections throughout the brain. Nicotine is not exactly the same chemically as acetylcholine, but can mimic its effects. Changeux’s lab has since focused on the workings of the nicotine/acetylcholine system, and he has attempted to explain how all such regulatory systems, working together, can produce the experience we call consciousness—as well as more abstract concepts like truth.

How, then, does the mass of cells in the brain produce our experience of sight, sound, and imagination? According to Changeux, the infant brain is not a blank slate, receiving all experience and instruction—both what it sees and how to think about it—from the outside. Nor is the infant brain preprogrammed, its reactions predetermined, unable to change itself and adapt. Rather, as Changeux began to hypothesize in the late 1970s, the brain, beginning in the embryo, produces, by means of genetic action, “mental objects of a particular type that might be called prerepresentations—preliminary sketches, schemas, models.”

According to this theory, spontaneous electronic activity in the brain, “acting as a Darwinian-style generator of neuronal diversity,” creates dynamic, highly variable networks of nerve cells, whose variation is comparable with the variation in DNA. Those networks then give rise to the reflex movements of the newborn infant. Over time the infant’s movements become better coordinated. Neural networks associated with more successful movements—such as grasping an object—are “selected”; that is, their activity is reinforced as their synaptic junctions become strengthened. As the child continues to explore his or her surroundings, Darwinian competition strengthens some of these transient networks sufficiently to make them relatively permanent parts of the child’s behavioral repertoire. Changeux calls the process, first elaborated in a 1976 paper, “learning by selection.”

Animals and infants conduct this miniature version of natural selection by means of what Changeux terms “cognitive games.” One well-known example concerns cries of alarm in African vervet monkeys. Adult monkeys use a simple but effective vocabulary of sounds that warn against danger: a loud bark for leopards, a two-syllable cough for eagles, and a hissing sound for snakes. Surprisingly, researchers found, baby monkeys hiss at snakes without explicit instruction. Changeux writes, “Snakes seem to arouse a sort of innate universal fear, which probably developed fairly early in the course of the evolution of the higher vertebrates.” When adult monkeys confirm the baby’s judgment with their own hisses, the infant’s genetically produced prerepresentation is rewarded and reinforced.

But baby monkeys require more explicit instruction in protecting themselves against predators, such as eagles, to which they have been less genetically conditioned. At first,

newborn monkeys react to any form that flies in the air, which is to say to the class of birds as a whole. Then, gradually, a selective stabilization of the response to the shape of dangerous species takes place…. If the first cry of alarm is sounded by one of the young, the nearest adult looks up. If it sees a harmless bird, it does not react. But if the young monkey has spotted a martial eagle, the adult reacts by emitting a cry of alarm that confirms the presence of danger…. The adult’s cry of alarm validates a pertinent relationship between shape and sound that is established in the brain of the young monkey.

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