Tracing human memory with the help of a fruit fly

Ron Davis, Chairman of the Department of Neuroscience at Scripps Florida

You might not think that an obsession with fruit flies is the kind of thing that gets someone a department chairmanship at a world-class research facility. But it won Ron Davis his job leading Scripps Florida's neuroscience department, and now his hard work has resulted in breakthrough findings in the field of human memory that could be just the tip of the iceberg.

It turns out that the genes involved in some fruit fly learning processes are remarkably similar in both structure and function to those in humans and other mammals.

Davis has been developing a cutting-edge method to target and manipulate specific fruit fly brain cells. This fall, that method resulted in a major finding. The team found one gene, called gish, whose mutations are responsible for olfactory learning – the link between smells and short-term memories.

"This is the first time we have a new memory and learning gene that lies outside what has been considered the most fundamental signaling pathway that underlies learning in the fruit fly," Davis said.

Impressed by these results, the National Institutes of Health is supporting a new three-year, 3.2 million dollar grant for Davis's lab to identify the full spectrum of genes involved in learning and memory in Drosophila, the common fruit fly.

"A large number of genes we expect to identify in [the fruit fly] over the next several years should, in fact, play analogous roles in human learning and memory," Davis said. "As a consequence, our discoveries could provide several new candidate genes that could become potential targets for the development of drugs to treat a range of cognitive disorders."

One of the team's major goals is to identify all gene products that have essential roles in this complex neurobiological process. Davis plans to screen more than 90 percent of the genome for genetic functions involved in acquisition, short-term memory stability, long-term memory, and retrieval.

His team will be using recently-developed, genome-wide RNAi transgene libraries of fruit fly genes. RNAi, or RNA interference, helps control the selection and activity of genes. These small RNAs can increase or decrease the activity of other RNAs by binding to them, helping direct gene expression and protecting cells against viral mutation.

These properties make RNAi valuable for the kind of advanced, large-scale screens developed by Davis and his colleagues. Because RNAi can shut down genes in the cell systematically, it can help identify various components involved in cell processes or a specific event such as cell division.

"We're still early in the process of making the connections between [fruit fly] memory and learning genes and the pathology of human disease," Davis said, "but it's already clear that many of these genes will provide potentially important insight into human brain disorders."