Thursday, December 9, 2010

To erase a bad memory, first become a child

Editorial: Troops need to remember

IT ADDS new meaning to getting in touch with your inner child. Temporarily returning the brain to a child-like state could help permanently erase a specific traumatic memory. This could help people with post-traumatic stress disorder and phobias.

At the Society of Neuroscience conference in San Diego last month researchers outlined the ways in which they have managed to extinguish basic fear memories.

Most methods rely on a behavioral therapy called extinction, in which physicians repeatedly deliver threatening cues in safe environments in the hope of removing fearful associations. While this can alleviate symptoms, in adults the original fear memory still remains. This means it can potentially be revived in the future.

A clue to permanent erasure comes from research in infant mice. With them, extinction therapy completely erases the fear memory, which cannot be retrieved. Identifying the relevant brain changes in rodents between early infancy and the juvenile stage may help researchers recreate aspects of the child-like system and induce relapse-free erasure in people.

One of the most promising techniques takes advantage of a brief period in which the adult brain resembles that of an infant, in that it is malleable. The process of jogging a memory, called "reconsolidation", seems to make it malleable for a few hours. During this time, the memory can be adapted and even potentially deleted.

Daniela Schiller at New York University and her colleagues tested this theory by presenting volunteers with a blue square at the same time as administering a small electric shock. When the volunteers were subsequently shown the blue square alone, the team measured tiny changes in sweat production, a well-documented fear response.

A day later, Schiller reminded some of the volunteers of the fear memory just once by presenting them with both square and shock, making the memory active. During this window of re-consolidation, the researchers tried to manipulate the memory by repeatedly exposing the volunteers to the blue square alone.

These volunteers produced the sweat response significantly less a day later compared with those who were given extinction therapy without any reconsolidation (Nature, DOI: 10.1038/nature08637).

What's more, their memory loss really was permanent. Schiller later recalled a third of the volunteers from her original experiment. "A year after fear conditioning, those that had [only] extinction showed an elevated response to the square, but those with extinction during reconsolidation showed no fear response," she says.
A year after conditioning, those whose memory had been manipulated showed no fear response

The loss in infant mice of the ability to erase a fearful memory coincides with the appearance in the brain of the perineuronal net (PNN). This is a highly organised glycoprotein structure that surrounds small, connecting neurons in areas of the brain such as the amygdala, the area responsible for processing fear.

This points to a possible role for the PNN in protecting fear memories from erasure in the adult brain. Cyril Herry at the Magendie Neurocentre in Bordeaux, France, and colleagues reasoned that by destroying the PNN you might be able to return the system to an infant-like state. They gave both infant and juvenile rats fear conditioning followed by extinction therapy, then tested whether the fear could be retrieved at a later date. Like infant rats, juvenile rats with a destroyed PNN were not able to retrieve the memory.

Since the PNN can grow back, Herry suggests that in theory you could temporarily degrade the PNN in humans to permanently erase a specific traumatic memory without causing any long-term damage to memory.

"You would have to identify a potential source of trauma, like in the case of soldiers going to war," he says. "These results suggest that if you inject an enzyme to degrade the PNN before a traumatic event you would facilitate the erasure of the memory of that event afterwards using extinction therapy."

For those who already suffer from fear memories, Roger Clem at Johns Hopkins University School of Medicine in Maryland suggests focusing instead on the removal of calcium-permeable AMPA receptors from neurons in the amygdala - a key component of infant memory erasure. Encouraging their removal in adults may increase our ability to erase memories, he says.

"There is a group who do not respond [to traditional trauma therapy]," says Piers Bishop at the charity PTSD Resolution. "A drug approach to memory modification could be considered the humane thing to do sometimes."

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