When Elvis released his first number-one country hit "I Forgot to Remember to Forget" in 1955, the song was more correct scientifically than he could have imagined. Humans need to forget as part of the brain's system for the management of memories acquired across a lifetime.

"Understanding the process of forgetting could have an enormous impact on how we treat a whole range of diseases," said the senior author. "Certain memories are intrusive and, with sufficient knowledge of how the brain forgets, we should be able to remove selective memories. Alternatively, we could find a way to inhibit forgetting in those suffering from memory disorders such as Alzheimer's disease."

The new study, published in the journal Neuron, uncovers a new aspect of how this process works. The results show that a protein called "Scribble" orchestrates the intracellular signaling processes for forgetting, joining several molecules to forge a pathway.

To conduct this research researchers turned to Drosophila, or the common fruit fly, a critical model for studying memory found to be highly applicable to humans.

By "knocking down" the expression of the gene that produces Scribble, the researchers produced flies that were able to remember twice as much as normal flies, simply because they failed to forget at the normal rate. The researchers also identified Scribble's crucial role in interacting with other key molecular players for forgetting within the fly brain.

They also show that Scribble interacts physically and genetically with Rac1, Pak3, and Cofilin within MBn, nucleating a forgetting signalosome that is downstream of dopaminergic inputs that regulate forgetting.

"What Scribble does is combine the Rac1 and dopamine pathways together into a single dynamic pathway that controls active forgetting," senior author said. "It orchestrates a series of molecules that are involved in this particular forgetting pathway, and there may well be others we have yet to discover."

"The Scribble protein is expressed in the same neurons that encode olfactory memories," said the study's first author. "We were able to show that it regulates memory by involvement in this particular forgetting pathway, an important biological process that has been surprisingly ignored."

http://www.scripps.edu/news/press/2016/20160602davis.html