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MIT scientists implant a false memory into a mouse’s brain

The hippocampus of a mouse brain, after the making of a memory. The cells glowing in red contain the memory of a particular environment and have been genetically tricked to be capable of being turned on with just brief pulses of light. (Courtesy of Xu Liu and Steve Ramirez)

Sometime soon, a lab mouse could wake up thinking he had snuggled up to a girl mouse the night before. But he hadn’t. The memory would be fake.

Scientists have successfully implanted a false memory into a mouse’s brain — a seemingly far-fetched idea reminiscent of a science fiction film.

“If mice had Hollywood, this would be ‘Inception’ for them,” said one of the lead researchers, MIT neuroscientist Steve Ramirez, whose study was published online Thursday in the journal Science.

Ramirez and his colleagues tagged brain cells associated with a specific memory and then tweaked that memory to make the mouse believe something had happened when it hadn’t.

Although implanting a memory won’t happen anytime soon in people, in principle, it should be possible to isolate a human memory and activate it at will, scientists said.

“We would have every reason to expect this would happen in humans exactly as it happened in mice,” said Michael J. Kahana, who was not involved in the study but is director of the University of Pennsylvania’s Computational Memory Lab.

Researchers said the ability to implant a false memory was a scientific milestone; Kahana called it a “technical tour de force.” The study’s authors said this type of research could one day help treat some emotional problems, such as post-traumatic stress disorder, which involves the intrusion of unwanted memories.

The first step in the mouse experiment took place last year when Ramirez and his colleagues isolated an individual memory in a mouse’s brain by tagging the brain cells associated with it and inducing recall of the memory at will by forcing those neurons to fire with light. In this new study, they artificially stimulated neurons to make associations between events and environments that had no ties in reality and, in essence, implanted a new, false memory.

They used a technique called optogenetics, which uses light to turn on and off activity of individual brain cells in a living animal. An optical fiber feeds light into the mouse’s hippocampus, the area of the brain that plays a prominent role in forming new memories.

False memories in humans often happen when a person swaps out one detail for another. Sometimes these mistakes are trivial, such as swearing that you left your keys on the kitchen table only to find them hanging in the garage. In a courtroom setting, a false eyewitness account can destroy an innocent person’s life.

Ramirez recounts a true story about an Australian psychologist who was arrested for a rape he did not commit. Physically, he fit the bill of the victim’s description, but he had a foolproof alibi. He was speaking on a live television show at the time of the rape — the same show, it turned out, the victim had been watching right before her attack. As a result, she described him as her attacker, even though it wasn’t possible.

Red room equals danger

In their experiment, the scientists implanted memories associated with certain rooms or chambers where they placed the mouse. Similar to a person visiting a friend’s apartment and forming a memory about his ratty couch and cramped bathroom, a mouse explores and takes mental note of a given chamber’s nooks and crannies.

Say a mouse gets put in a chamber with red walls. It is sniffing around, when suddenly it feels a mild shock zap its feet. When the mouse is dropped into the same red room the next day, even if there’s no shock, it recalls the unpleasant experience and freezes in fear.

After the jolt, “it formed a new memory that this chamber is a very dangerous place,” said senior author and MIT neuroscientist Susumu Tonegawa.

Next, Tonegawa and his colleagues wanted to find out if they could induce recollection of a memory at will by forcing the neurons associated with that memory to fire. They put the mouse in a different, benign blue room, where it boldly moved about and probed the new surroundings as usual. But once the scientists forced those neurons to activate, the mouse immediately remembered the bad experience and froze.

“Now that we can reactivate a memory, can we tinker with that memory, maybe making it into a false memory?” Ramirez asked.

Putting a new mouse in the red chamber, they let it recognize the room as harmless. The following day, they had it explore a blue-walled chamber, and then gave it a mild jolt while simultaneously inducing recall of the red room. This was meant to artificially associate the memory of the shock-free red room with the fear of being shocked.

On the third day, Tonegawa and his colleagues wanted to see whether this false association had successfully been implanted. They placed the mouse in the red room, where it froze even though nothing bad had ever happened to it there. A false memory had been formed and recalled.

Process of evolution

So why is the brain, whether rodent or human, so susceptible to muddling up the past?

“My hypothesis is that, actually, this is a trade-off of other functions that the human brain acquired during evolution,” Tonegawa said. “Human beings are very imaginative and creative animals.”

Ramirez agrees: “Memories are remarkable, and they are nature’s only real-time machine that exists right now. But sometimes those details, the bits of information in your brain, can get misincorporated and misassociated with other bits.”

Because he finds implanting fear “kind of depressing,” Ramirez next wants to try to implant pleasurable memories in mice, such as thoughts about rodents of the opposite sex.



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