Source: New York Times
Date: 27 August 27, 1991

Pain and Learning May Be Close Cousins In Chain of Evolution


AS the school year draws nigh, students who loathe the thought of confronting organic chemistry and the unabridged work of Thucydides may not be surprised to hear that learning and pain could have a common evolutionary origin.

Scientists studying the nervous system of a slimy marine mollusk have found that the snail's nerve cells display the same physical changes when they are injured as they do after the creature has learned a new behavior.

The results suggest that the brain uses a similar biochemical mechanism for mastering a task as it does to avoid further harm after injury.

By this notion, the brain's ability to learn and remember may have evolved from the more primitive sensation of pain, a critical reaction to injury that helps assure an animal will zealously guard its wounds until they are healed.

"Our hypothesis is that the simple mechanisms for responding to cell injury are expressed in other forms as a mechanism for learning and memory," said Dr. Edgar T. Walters of the University of Texas Medical School at Houston, who reported the new results in a recent issue of the journal Science.

Other researchers studying the molecular basis of learning said they were intrigued by the new report, but not yet entirely convinced by the evidence that there was an evolutionary link between pain and learning. 'A Little Bit Further Out'

"Walters is a rather creative guy, and he is very thoughtful," said Dr. Eric R. Kandel of the Columbia University College of Physicians and Surgeons in New York, one of the nation's leading neurobiologists, who had been Dr. Walters's graduate thesis adviser. "But some of the things he does are a little bit further out than others, and this is one of them."

Dr. Walters was led to his unorthodox theory by a consideration of several disparate observations others have made in the past. Researchers analyzing the brains of cats and rats have found that after the creatures have been conditioned to respond to stimulation or to complete a task, like running a maze, nerve cells in some regions of the brain exhibit characteristic changes. Most notably, they become far more likely to fire off electrochemical signals that help pass information from one neuron to the next.

In unrelated work, doctors have noticed that in people whose peripheral nerves have been injured, the healthy nerve cells surrounding the wounded nerves form what is called a neuroma, a cluster of neurons that is extremely sensitive to the slightest sensation or motion.

"People who have neuromas can hardly stand to have anybody touch the skin near it," said Dr. Walters. "If they're touched, the pain is excruciating."

Dr. Walters wondered if there was any connection between the hyperexcitability of cells in a neuroma, and the electrical vigor of nerve cells that participate in memory and learning.

To test the notion, he and his colleagues turned to a snail called Aplysia californica, or the sea hare. The creatures -- which have only a vestigial shell and thus resemble giant slugs more than they do snails -- are found around West Coast beaches, where they feast so voraciously on seaweed that they can reach up to 15 pounds and two feet in length. "They spend all their time eating and copulating," said Dr. Walters. "Their only real problem appears to be avoiding neurobiologists." Guarding the Siphon

Because its nerve cells are large, accessible and relatively few in number, Aplysia has become a favored experimental organism for the analysis of the molecular basis of learning and memory. Dr. Kandel and others have demonstrated that the mollusk can learn to respond to outside stimulation in a distinct manner depending on the nature of the stimulation.

The neurobiologists study a particular snail behavior, its reflexive withdrawal of its protruding siphon, an organ used for expelling water and feces. In general, a mollusk does not like to have its siphon molested, and it will instinctively pull in the little flange-like projection when it is poked. But if its siphon is touched gently and repeatedly, the mollusk becomes habituated, and it will stop bothering to respond by a reflexive drawing in.

If, on the other hand, a mild shock or a hard pinch is applied to the siphon a few times, the Aplysia will become sensitized: it will start yanking in its siphon quickly and violently, even at the tiniest and most harmless of nudges.

In either case, the snail has learned a new response to the outside world, and the basis of either adaptation can be seen in the sensory nerve cells that control the muscles of the siphon. When habituation occurs, the nerve cells undergo extensive biochemical changes that make them less likely to fire off electrochemical signals to the muscles and surrounding neurons, and thus less likely to send along the message that the siphon should be withdrawn.

But in an Aplysia that has been lightly shocked a few times, the sensory nerve cells become hypervigilant, able to fire off as much as two or three times the number of nerve impulses as a mollusk nerve cell would ordinarily. The result is that the snail needs almost no touch at all before its nerve cells start firing wildly and commanding the siphon muscle to withdraw.

Whether dampened or heightened, the changes in the nerve cells last for hours or weeks, indicating that a genuine memory in the Aplysia nervous system has been formed.

To see if injury had a similar impact on Aplysia nerve cells as learning, Dr. Walters studied the same class of sensory neurons examined in previous memory experiments. He put the creatures under anesthesia and then crushed parts of their nerve cells. The cells were not killed, but were merely exceedingly damaged.

Four days later, he and his co-workers examined the changes in the wounded nerve cells and discovered that they resembled those of sensitized but unharmed nerve cells that have been trained to be particularly diligent about jerking in the snail's siphon.

The injured nerve cells were three times more likely to fire off impulses to muscles and adjoining nerve cells compared with uninjured nerve cells. What is more, nerve cells immediately surrounding the point of crushing also became more electrically charged.

"This was an entirely unexpected result that nobody has observed before," he said.

Dr. Walters believes that for a nerve cell to become hyperexcitable when it or its neighbor has been injured makes evolutionary sense. By becoming pitched and ready to respond to even a hint of additional stimulation, the nerves in the damaged area can help prevent further destruction. The excitable nerves can serve as amplifiers, turning a minor signal from the outside into an almost deafening alarm to the brain.

"It signifies to the brain, watch out, somebody is touching or threatening my wound," he said. "This tells the brain that it had better take urgent emergency efforts to protect the wounded area."

Dr. Walters thinks that the most primitive organisms had to possess a built-in mechanism that would focus the body's attention on protecting a wounded area. And that mechanism had to have staying power, he said, to assure that the creature took care to keep the wound guarded during recovery.

As creatures evolved, he said, the same pathway for amplifying a pain signal also proved to be a useful way of changing nerve cells during learning, allowing them to adapt biochemically to experience.

"Evolution is opportunistic," he said. "It takes advantage of pre-existing mechanisms." The plasticity of nerve cells probably developed to protect against a wound, he said, but eventually that plasticity may have served a further purpose, allowing a creature to learn from experience and perhaps avoid getting wounded in the first place.

Diagrams: "Theory of Learning at a Snail's Pace" After repeated gentle stimulation of snail's siphon, sensory nerve emits weak retraction signal; shock or injury seem to "teach" it to emit stronger signal. (Sources: De. Edgar T. Walters; "Microbiology of the Cell" (Garland)

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