Long-term memory controlled by molecular pathway at synapses

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Even for a fruit fly, learning and memory are important adaptive tools that facilitate survival in the environment. A fly can learn to avoid what may do it harm, such as a flyswatter, or in the laboratory, an electric shock that happens when it smells a certain odor.

Now Harvard University biologists have identified a molecular pathway active in neurons that interacts with RNA to regulate the formation of long-term memory in fruit flies. The same pathway is also found at mammalian synapses, and could eventually present a target for new therapeutics to treat human memory loss.

“It has been known for some time that learning and long-term memory require synthesis of new proteins, but exactly how protein synthesis activity relates to memory creation and storage has not been clear,” says Sam Kunes, professor of molecular and cellular biology in Harvard’s Faculty of Arts and Sciences. “We have been able to monitor, for the first time, the synthesis of protein at the synapses between neurons as an animal learns, and we found a biochemical pathway that determines if and where this protein synthesis happens. This pathway, called RISC, interacts with RNA at synapses to facilitate the protein synthesis associated with forming a stable memory. In fruit flies, at least, this process makes the difference between remembering something for an hour and remembering it for a day or more.”

Together with lead author Shovon Ashraf, a postdoctoral researcher in Harvard’s Department of Molecular and Cellular Biology, and Anna McLoon ’04 and Sarah Sclarsic ’06, Kunes found that messenger RNA (mRNA) – a genetic photocopy that conveys information from DNA to a cell’s translation machinery – is transported to synapses as a memory begins to form. This mRNA transport, and the protein synthesis that follows, are facilitated by components of the RISC pathway, which use very short RNA molecules called microRNAs to guide their activity. One of these RISC proteins, called Armitage, appears to be a critical regulatory molecule in long-lasting memory formation, and has to be destroyed at particular synapses in order for protein synthesis to occur there.

The findings were presented on the Web site of the journal Cell.