Palaces For The People
Saturday, December 27, 2003
Research With Sea Slugs and Yeast May Explain How Long-Term Memories Are Stored

This supports my hypothesis that prions are engrams for memory storage.

Research With Sea Slugs and Yeast May Explain How Long-Term Memories Are Stored

Published: December 25, 2003

By tinkering with yeast and sea slugs, scientists have found a surprising possible explanation for the way the human brain stores long-term memories.

Those lowly creatures possess an unusual protein that exists in two shapes. In one shape, the protein is sluggish or inactive. In its second shape, the protein perpetuates itself indefinitely but can also harmlessly switch back to the inactive form.

Researchers believe that in higher organisms the same protein may exploit this second shape to confer lasting stability to sites on brain cells, called synapses, that store the memories of a lifetime.

Surprisingly, the shape-shifting protein in yeast and slugs has all the hallmarks of another protein, the infamous prion, found in humans and other animals. Such prions also assume two shapes. One serves a normal function in the brain. The second sets into motion a runaway process that converts normal prions into a toxic form. As a result, deadly clumps of protein leave holes in the brain and cause disorders like mad cow disease.

The disease-causing prion and the memory-storage protein are not identical, said Dr. Eric R. Kandel, a neuroscientist at Columbia University who shared the 2000 Nobel Prize in Physiology or Medicine for his research on memory formation. But they share attributes that make prionlike behavior a perfect mechanism for storing memories.

With experience and learning, new synapses are formed and others are strengthened, Dr. Kandel said. Indeed, the mechanisms explaining the way short- and long-term memories are formed have largely been worked out. But the questions of how long-term memories are actually stored and what keeps synapses from losing their connectivity under the onslaught of constant cellular remodeling are outstanding mysteries in biology.

The first clue for the hypothesis came from yeast, which have their own version of a prion. It has several functions, none, of course, related to brains.

Still, researchers in the laboratory of Dr. Susan Lindquist, director of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology, have used yeast prions to explain the way different prion strains arise and other aspects of prion biology.

In studying yeast prions, Dr. Lindquist and her colleagues found a specific region of the protein that is responsible for its ability to adopt two shapes. But the second shape in yeast is inactive and does not cause disease, as it does in higher organisms.

Meanwhile, Dr. Kausik Si, a postdoc in Dr. Kandel's laboratory, was studying a protein in sea slug neurons with the ungainly name, cytoplasmic polyadenylation element binding protein, or C.P.E.B. He noticed that the end of that protein contains a region that looks much like the region that permits shape shifting in yeast.

The two laboratories mounted a series of experiments that are described in the Dec. 26 issue of the journal Cell. Basically, the researchers fused the end of the slug's C.P.E.B. protein into yeast to see what would happen.

Recall that in normal yeast, the prion is inactive when it assumes a self-perpetuating shape. The opposite is true in the fused hybrid. There, the self-perpetuating prion is highly active. It makes other prions adopt its shape without producing toxicity. It induces protein synthesis using molecules known to be involved in memory formation and does so with pinpoint precision, as if marking synapses for permanence.

These prionlike traits make C.P.E.B. an ideal candidate for keeping synapses permanently altered, as long as a memory lasts, Dr. Kandel said.

To find out if a new kind of prion is what enables memories to be stored, researchers have begun new experiments on flies and mice.

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