Memo From Protein to Brain: Forget It!

The common notion that memories "fade" with time implies that memory loss is something that just happens. But a new study suggests that the reality may be quite different: At least one brain protein seems to be actively engaged in discarding memories. The new results could help explain why memory worsens with age and how the brain tosses out information it doesn't need to remember.

From all the sensory information that bombards it, the brain must choose what to remember. It does this with the help of two classes of brain proteins with opposing functions, creating a balance between activation and inhibition of biochemical processes. Neurobiologist Isabelle Mansuy and her colleagues at the Swiss Federal Institute of Technology in Zurich investigated one member of one of these protein classes, called protein phosphatase 1 (PP1). They tested whether PP1 was involved with forgetting by genetically engineering mice to express a molecule that blocks PP1 activity. Then the group gave memory drills to these animals as well as normal ones.

To familiarize the mice with certain objects, they placed the mice in a box with three different objects for 5-minute sessions, separated by breaks of either 5 or 15 minutes. After the set of sessions was complete, the researchers found that normal mice remembered the objects best when they got the longer breaks (suggested by the animals' investigation of new objects, but not ones they'd already seen). But mice without PP1 learned equally well when the breaks were only 5 minutes, suggesting that in normal mice, the longer breaks give the brain a chance to block PP1 and cement memories.

Mansuy's team also found that inhibiting PP1 reverses the memory decline associated with old age. They tested how well mice aged 15 to 18 months--the equivalent of an elderly human--remembered the location of an underwater platform. As the researchers report in the 29 August issue of Nature, normal mice forgot the platform after only a day, whereas mice that block PP1 activity recalled the platform's location even 4 weeks later. These results imply that memory declines with age in part because of an increase in PP1 compared to the proteins that aid memory, and that the decline is reversible by inhibiting PP1.

"One of the blackest of all boxes in science is being opened," says neuroscientist Alcino Silva of the University of California, Los Angeles, referring to brain processes that govern cognition. The results, he says, demonstrate that forgetting is something the brain does actively.

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Isabelle Mansuy's lab
Alcino Silva's lab

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