For those haunted by thoughts of an old flame or a tragic accident, the chance to selectively erase memories might be tempting.

Now scientists have moved a step closer to that possibility by wiping away a month-old memory in genetically engineered laboratory mice, while leaving other memories unchanged.

The researchers boosted levels of a protein called α-CaMKII involved in memory storage and retrieval, just as mice recalled the pain of receiving a light shock. This had the effect of dispelling the memory.

“I don’t think it’s possible to use our method in humans, whether it’s now or in the future,” says Joe Tsien, a neuroscientist at the Medical College of Georgia in Augusta. “But it does suggest that perhaps you can look into downstream targets [of α-CaMKII]. Maybe some pharmaceutical company is looking at that.”


Shattered belief

Tsien’s experiments aren’t the first to raise the prospect of selective memory erasure.

Several years ago, researchers showed that injecting mice with a drug that stops new proteins from forming can block an old memory as it is recalled.

And last year, another team found that inhibiting a specific protein can erase old memories, even without recalling them.

These experiments have helped shatter the century-old belief that memories are an indelible anatomical feature of the brain, says neuroscientist Todd Sacktor, of SUNY Downstate Medical Center in Brooklyn, New York. Rather, memories are the stuff of molecular connections, constantly built and destroyed by specific enzymes.

“There are actually key molecules that have specific role in long-term memory,” he says. “It’s a real big shift in thinking.”

Shock treatment

Based on previous experiments that showed that α-CaMKII was important to a cellular phenomenon thought to underlie memory formation, Tsien’s team bred mice engineered to make extra levels of the enzyme. His team could return their α-CaMKII levels to normal by giving the mice a drug that blocked only the engineered copy.

To test the effect of the change, Tsien and colleagues at the East China Normal University in Shanghai gave mice a slight shock in a training chamber while playing a loud tone.

With thoughts of a jolt fresh in their brain, mice with normal levels of α-CaMKII froze up when they returned to the chamber an hour later, while mice with boosted levels remained calm.

Even a month after the shock – enough time for mice to store the memory for good – cranking up α-CaMKII eroded all memories of the shock treatment, Tsien’s team found.

The memory also seemed completely lost, not temporarily unavailable. Six weeks after the initial conditioning and two weeks after the initial erasure, engineered mice treated so they expressed normal levels of α-CaMKII could not retrieve memories of the shock.

Value of recall

Tsien’s team is still trying to explain how turning up a single protein can erase specific memories, but he thinks the protein weakens brain cell connections that were built up when the memory was first made.

“This paper is a real revolution in how we think about long term memory,” says Sacktor, who last year showed that blocking an enzyme called PKM-zeta erases long-term memories in rats, while leaving their ability to form new ones unchanged. It is not yet clear which route to memory removal will prove most useful in humans, he says.

Tsien, however, cautions against applying his team’s results to expunging thoughts of broken hearts or limbs. “All memories, even very painful emotional memories, have their purposes. We learn from those experiences to avoid making the same kind of mistake.”

Journal reference: Neuron (DOI: 10.1016/j.neuron.2008.08.027)

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