Pavlov’s flies: Researchers identify fruit fly memory mutants

Broad implications seen for treating Alzheimer’s and other human diseases

By teaching fruit flies to avoid an odor and isolating mutant flies that can’t remember their lessons, researchers at Cold Spring Harbor Laboratory in New York have identified dozens of genes required for long-term memory.

In the same study, using DNA chip technology, the scientists identified another large group of candidate memory genes that are either switched on or off in the fly brain during memory formation.

The study is significant in part because many of the fruit fly genes it uncovered have counterparts in humans. Because these genes might be involved in human learning and memory, they may be important for understanding human memory deficit disorders such as Alzheimer’s disease. Moreover, the genes are potential targets for the development of therapies to treat such disorders. The study (available on request) appears in the February 18 issue of Current Biology (illustrations also available on request).

Interestingly, an overlapping set of seven candidate memory genes appeared in both the behavioral screen and the DNA chip analysis. Additional experiments confirmed that when genes identified by the DNA chip approach are mutated or switched off in flies, the resulting flies fail to form long-term memories.

The study, by Cold Spring Harbor Laboratory neuroscientists Tim Tully and Josh Dubnau, reveals new roles for nearly 100 genes in memory, as well as a role in memory for a specific subset of genes that is believed to act to restrict protein production to particular regions within brain neurons.

The behavioral screen for memory mutants uncovered 60 genes, and the DNA chip analysis yielded 42 genes. Considering the seven genes that appeared in both groups, the study identified a total of some 92 unique genes likely to function in learning and memory at some level.

“The brain of the fly works very much like the brain of other animals, including humans. Flies are capable of learning just like Pavlov’s Dogs,” says Tully. “In fact, because our fruit fly memory mutants were found using a behavioral approach very similar to Pavlov’s, our flies have come to be known as Pavlov’s Flies.”

After ringing the dinner bell and presenting his dogs with food several times over many days, the Russian psychologist Ivan Pavlov (1849-1936) found that eventually, his dogs would display dinnertime behavior (drooling, excitement) on just the sound of the bell.

In a fascinating and entertaining essay (available on request) that accompanies the published study, Tully describes how in 1992 he traveled to the Pavlov Institute in Koltushi, Russia to find the names of Pavlov’s Dogs with the intention of naming his fruit fly memory mutants after the dogs. This despite the fact that at that time, he had few such fly mutants, and had been able to find the name of but one of Pavlov’s Dogs, Bierka.

After several dead ends, and on the final day of his visit, Tully was invited for a private tour of Pavlov’s home. There he struck gold when the curator showed him a photo album inside which were photographs of forty of Pavlov’s Dogs, along with their Russian names (e.g. Rosa, Mirta, Norka, Trezor, Visgun, Jurka, Jack, John. Photographs and complete list of names available on request).

Previous studies by Tully and Jerry Yin have shown that boosting the expression level in the fly brain of a gene called CREB provides flies a form of photographic memory. Preliminary research now indicates that drugs which boost the expression level of the mouse CREB gene can improve memory in mice. Human memory, particularly in patient’s with Alzheimer’s disease, may well be improved by the same kind of drug