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New studies erase traumatic memories in mice

What if wiping out a traumatic memory were as simple as taking a few breaths? What if, with the flip of a switch, a frightening recollection could lose its nightmarish feeling or a pleasurable memory could begin to feel scary?

Memories can seem inviolable; they shape our personalities and world views, and help define who we are. But a growing body of work in neuroscience is showing that, at least in rodents, triggering the right brain circuits at the right time can radically alter remembrance of things past. Although the research is early and still being tested in animals with simple brains and rudimentary fear memories, they hope similar approaches can be eventually harnessed to help treat devastating conditions in people, such as post-traumatic stress disorder or addiction.

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In research published Wednesday in the journal PLOS ONE, McLean Hospital researchers took rats that had learned to fear a tone because it was followed by a foot shock and erased the negative memory, by having them breathe xenon gas. In a separate study, Massachusetts Institute of Technology scientists reported in the journal Nature they were able to use cutting-edge genetic tools to alter the emotional context of a memory, allowing them to replace the negative memory of receiving a mild electric shock with the pleasurable one of mingling with mice of the opposite sex.

That adds to a body of research from MIT over recent years that has shown that administering a drug can wipe out a negative memory in mice, or that it is possible to trigger an existing memory or plant a false one using genetic manipulation.

Edward Meloni, an assistant psychologist at McLean who led the xenon gas research, said that there’s growing interest in the process of “reconsolidation” when a memory is replayed in the mind.

“Every time you reactivate a memory -- that is, recall it -- it’s susceptible to modification,” Meloni said. “The analogy is you hear about people who give eyewitness testimony and their testimony can change over time. What the brain is doing is updating the memory each time it’s recalled and introducing new little facts.”

Meloni and his colleague Marc Kaufman, director of the Translational Imaging Laboratory at McLean, hoped to exploit that reconsolidation period by erasing the memory altogether. There was evidence that xenon gas interfered with a cellular signaling pathway in the brain that was relevant for learning and memory, and they wondered if administering the gas when a memory was being reconsolidated would interfere with how it was saved in the brain.

First, they trained mice to fear the sound of a tone because it was followed by a shock on the foot. The memory of the shock caused the mice to freeze after they heard the sound. Then, they reactivated the memory by sounding the tone. Instead of a shock, the mice breathed xenon gas for an hour. Afterward, they froze much less often when they heard the tone -- the memory was gone. Xenon is colorless and odorless, and is used in people as an anesthetic and in imaging experiments.

The MIT research used a technique called optogenetics, which involves laser light and genetic tweaking, to activate specific memories when mice were having scary or pleasurable experiences . They found that they could alter the valence of the memory -- making something the mice previously feared into something they sought out, or the reverse.

Optogenetics is far from being applicable to humans since it involves genetically modifying brain cells and snaking a fiber optic cable into the skull, but the insights gained may help elucidate the circuitry underlying memory and may give clues about how to tune therapies that could reinforce or alter the emotion associated with different recollections.

The McLean Hospital research could reach a clinical trial much sooner. Xenon gas is already administered to people, and the researchers at McLean are trying to raise funds to support a safety study in which they can test whether people without mental illness can have simple fearful memories extinguished as easily as the mice did.

People trained to associate a flash of blue light with a mild electrical shock begin to sweat in anticipation after they see the light. If the researchers find that they can erase that involuntary fear response by having people breathe xenon gas, they may then extend their work to the much more complicated problem of trying to erase painful memories in patients suffering from post-traumatic stress disorder.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.
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