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Tricking memory in lab animals stokes hope for PTSD

By Sharon Begley

NEW YORK (Reuters) - The frailty of remembrance might have an upside: When a memory is recalled, two research teams reported on Wednesday, it can be erased or rewired so that a painful recollection is physically linked in the brain to joy and a once-happy memory to pain.

While lab rodents were used in the research, it adds to growing evidence that the malleability of memory might be exploited to treat disorders such as post-traumatic stress.

In both studies, scientists focused on a phenomenon called reconsolidation. Discovered in the 1990s, it refers to the fact that when a memory is retrieved, its physical manifestation in the brain is so "labile," or changeable, that it can be altered. False memories can form, and the associated emotions can flip.

"Recalling a memory is not like playing a tape recorder," said Susumu Tonegawa of the Massachusetts Institute of Technology, who led one of the studies. "It's a creative process."

The MIT team decided to see how creative. They gave male mice a small electric shock when the animals wandered into one part of a cage, creating a memory linking that place to pain. In a different part, mice got to cavort with females, so they remembered that spot quite fondly.

The mice had been engineered so specific brain neurons could be activated with light, a technique called optogenetics. Using lasers, the scientists reactivated the where, what and when of the memories, which are encoded in the hippocampus.

While the shock memory was active and labile, the mice got to play with females. While the memory of socializing was active, they got a shock.

That changed brain wiring, the scientists reported in the journal Nature. The memory of the shock became physically connected to neurons encoding pleasure; the memory of socializing connected to neurons encoding fear.

"We could switch the mouse's memory from positive emotions to negative, and negative to positive," Tonegawa told reporters.

More research is needed before anything similar could be used in people, MIT's Roger Redondo said, "but the circuits appear to be very similar" as in mice.

In a separate study, researchers at Boston's McLean Hospital also exploited the malleability of reactivated memories to erase them completely.

After training rats that a flash of light precedes a shock, the researchers turned on the light, reactivating the memory. They immediately gave the animals xenon gas, an anesthetic that blocks molecules involved in memory formation.

That apparently jammed the machinery needed for memory reconsolidation, psychologist Edward Meloni and colleagues reported in the journal PLOS One: The rats forgot that light precedes a shock. Similarly trained rats not given xenon remembered just fine.

Psychologist Elizabeth Phelps of New York University called both studies "interesting advances."

But clear ethical issues involved in manipulating human memory remain, even for therapeutic purposes.

"I think we are still a long way from translating this research to good clinical interventions," since memories that contribute to PTSD are "likely much more complex" than in mice and rats, Phelps said.

(Reporting by Sharon Begley; editing by Gunna Dickson)

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