A Protein That Aids Forgetting

The act of forgetting is essential for clearing space in the brain for new information, yet the biochemistry underlying this process has never been ascertained. Now, Yi Zhong, a neuroscientist at Cold Spring Harbor Laboratory, in New York, and coworkers have for the first time identified a molecule that the brain uses to erase short-term memory (Cell 2010, 140, 579).

The molecular eraser is Rac, a small G-protein previously known for its participation in signaling pathways that control cellular processes such as transcription and cytoskeletal organization. The researchers believe Rac acts through the protein cofilin to control polymerization of actin, which affects the structure and interaction of neurons and, hence, memory.

Zhong and colleagues at Beijing's Tsinghua University "have crystallized the notion that the brain mechanisms for remembering are balanced by a mechanism for active forgetting," notes Ronald L. Davis, a neuroscientist at Scripps Research Institute Florida, in Jupiter. "Moreover, they have ushered in a completely new line of research—the cell biology of active forgetting—by identifying Rac as critical for active forgetting," Davis writes in an accompanying commentary.

Working with the fruit fly Drosophila melanogaster, an organism often used for neuroscience lab studies, the researchers found that ramping up Rac activity accelerates decay of short-term memory. In contrast, blocking Rac's activity causes memories that normally last just a few hours to endure for more than a day. Zhong speculates that long-term memory, which is stored in a different part of the brain, isn't affected by Rac because the protein's pathway doesn't operate in that brain region.

Because Rac is found in all organisms, these findings might be relevant for humans, Zhong says. If so, the Rac pathway could serve as a target for enhancing memory or erasing unwanted bad memories.

Of course, the Rac pathway is only one of the biochemical factors that influence memory. That means that people's different memory capabilities might derive not only from differing powers of forgetting, Zhong says, but also from differing powers of memory formation and retrieval.