Memories might be made of this: closing in on the biochemistry of learning

Science News, May 25, 1991 by Carol Ezzell

Experiments at Alkon's laboratory back up this scenario, however. In the February 1990 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol. 87, No. 4), Alkon and several co-workers report the results of injecting dye into light-receptor cells of trained and untrained snails. The dye revealed that the neurons of snails trained to associate light and shaking had fewer and more condensed branches than did those of untrained snails, suggesting that learning could reroute a nerve cell's branching.

Such rerouting should be reflected in fluctuations in the shipment of new cell membrane from the body of the cell to the branch tips, Alkon reasoned. Last year, Simon Moshiach from Alkon's lab, together with Nelson and Sanchez-Andres, demonstrated just such a change. With one squirt of G protein extracted from a snail, they slowed the flow of new protein globules along the axon -- the long "arm" that transmits outgoing messages -- of a large nerve cell taken from a crab.

Although Alkon contends that long-term memory probably requires changes in neuron structure, he also finds evidence that PKC is involved. Working with Matzel, now at Rutgers University in New Brunswick, N.J., he turned up evidence that PKC's effects can persist for weeks after H. crassicornis has learned.

Matzel trained the snails with just enough paired cycles of light and shaking that they learned to associate the two stimuli. He did not repeat the cycles over and over to reinforce the animals' memories, however. After about one week, the snails forgot the association: Light alone no longer caused their feet to tense. But when Matzel retrained the animals after waiting two weeks, he found that they could relearn the association after just a handful of trials.

"Even though they had forgotten, they retained some memory, because they relearned much more quickly," Alkon says.

To see if PKC had a hand in this effect, Matzel studied light-receptor cells taken from the eyes of snails that had forgotten their training. If he jolted the cells with a shot of calcium, they clamped down their potassium channels just as they would have if they had learned. But if he also added chemicals that blocked PKC, the potassium channels stayed open. "That's good evidence for long-lasting involvement of PKC in learning," Alkon argues.

With increasing evidence linking PKC to learning and memory in snails, Alkon's team began looking for a similar link in higher animals.

In 1988, Alkon's co-worker Barry Bank, with colleagues from NINDS and Yale University, used a radioactive stain to trace the activation of PKC in rabbits. They found that rabbits trained to associate a particular tone with a mild electrical shock near their eyes eventually learned to drop a protective membrane over their eyes whenever they heard the tone. The stain revealed that the trained rabbits harbored increased levels of PKC in the hippocampus of the brain. Previous studies involving animals and humans with hippocampal injuries had shown that this area of the brain is crucial to maintaining memory for many days.