Selectively Deleting Memories

Amping up a chemical in the mouse brain and then triggering the animal's recall can cause erasure of those, and only those, specific memories, according to research in the most recent issue of the journal Neuron.

While the study was done in mice that were genetically modified to react to the chemical, the results suggest that it might one day be possible to develop a drug for eliminating specific, long-term memories, something that could be a boon for those suffering from debilitating phobias or post-traumatic stress disorder.

For more than two decades, researchers have been studying the chemical--a protein called alpha-CaM kinase II--for its role in learning and memory consolidation. To better understand the protein, a few years ago, Joe Tsien, a neurobiologist at the Medical College of Georgia, in Athens, created a mouse in which he could activate or inhibit sensitivity to alpha-CaM kinase II.

In the most recent results, Tsien found that when the mice recalled long-term memories while the protein was overexpressed in their brains, the combination appeared to selectively delete those memories. He and his collaborators first put the mice in a chamber where the animals heard a tone, then followed up the tone with a mild shock. The resulting associations: the chamber is a very bad place, and the tone foretells miserable things.

Then, a month later--enough time to ensure that the mice's long-term memory had been consolidated--the researchers placed the animals in a totally different chamber, overexpressed the protein, and played the tone. The mice showed no fear of the shock-associated sound.

But these same mice, when placed in the original shock chamber, showed a classic fear response. Tsien had, in effect, erased one part of the memory (the one associated with the tone recall) while leaving the other intact.

"One thing that we're really intrigued by is that this is a selective erasure," Tsien says. "We know that erasure occurred very quickly, and was initiated by the recall itself."

Tsien notes that while the current methods can't be translated into the clinical setting, the work does identify a potential therapeutic approach. "Our work demonstrates that it's feasible to inducibly, selectively erase a memory," he says.

"The study is quite interesting from a number of points of view," says Mark Mayford, who studies the molecular basis of memory at the Scripps Research Institute, in La Jolla, CA. He notes that current treatments for memory "extinction" consist of very long-term therapy, in which patients are asked to recall fearful memories in safe situations, with the hope that the connection between the fear and the memory will gradually weaken.

"But people are very interested in devising a way where you could come up with a drug to expedite a way to do that," he says. That kind of treatment could change a memory by scrambling things up just in the neurons that are active during the specific act of the specific recollection. "That would be a very powerful thing," Mayford says.

But the puzzle is an incredibly complex one, and getting to that point will take a vast amount of additional research. "Human memory is so complicated, and we are just barely at the foot of the mountain," Tsien says.

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