Creating False Memories in Mice Brains—and in Yours

It takes a tricky bit of neural cross-wiring to make you remember things that never happened

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Every memory you ever had is in some respects a hallucination. You can see a scene, feel a feeling, even smell a smell at a time and in a context in which they didn’t occur at all.  That’s both good and bad—good because it speaks to an impressively powerful sense of recall; bad because with a little manipulation, the same brain cells can fire in the same way to create illusions of events that never occurred at all.

False memories can make a hash of a lot of things: criminal trials rise and fall on them, handshake agreements collapse over competing memories of who said what to whom. What has never been clear is the exact mechanism behind them. If you could spot where a false memory lives in the brain would it look the same as a real memory? Worse, if you know that particular site, could you manipulate it in some way to implant memories of your choosing in the brain of someone else? According to a new study in Science—that was thankfully conducted only in mice—the answer to both questions is yes.

As with humans, the central clearinghouse of memories in mice is the hippocampus, a small, sea-horse shaped structure that gathers in sensory streams from all over the brain, then integrates and prepares them for either short-term or long-term storage. In the new research, a team of investigators from MIT first identified a particular subset of cells in a hippocampal sub-region called the dentate gyrus (DG) that are particularly associated with forming contextual memories—exactly where a reward or a danger was encountered in the past so those places can be sought out or avoided in the future. The researchers then did a little manipulating of the DG with the help of a relatively new technique known as optogenetics.

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First they isolated a common adenovirus—usually associated with upper respiratory infections— then altered it by adding the genetic coding for channelrhodopsin, a light-sensitive pigment. Memory-related brain cells that have recently been active can easily be infected by the altered adenovirus; those that have been dormant for a while can’t. The scientists then allowed mice to explore a box within their cage area and afterwards, injected the adenovirus into their hippocampi, ensuring that the cells that preserved the memory of the chamber would be infected.  “We controlled the window of time in which the memory would be formed,” says MIT neuroscientist and lead author Steve Ramirez, “then we identified and tagged the cells involved in representing, say, a blue box.”

That memory was a benign one, but the next box—a red one—was less so. In that enclosure, the floor was electrified and the mice received a mild but painful electrical shock to their feet. When they were returned to the blue box, they would freely explore it, but when placed back in the red one, they would  freeze in place—a behavior most animals, including humans, exhibit when they sense possible danger.

All that so far is pretty typical mouse behavior. Finally, however, Ramirez and his colleague threaded fine optical fibers into the brains of the mice and returned them to the red box—the dangerous one. They then stimulated the DG region of the hippocampus with light. Most of the cells in that area would not react, but the ones that had taken up the channelrhodopsin would be awakened. That, in turn, would link the fear of the red box with the memory of the blue box. The result: when the mice went back to the blue box they froze there too.

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“They appeared to be recalling being shocked in the blue box, even though that had never happened,” says Ramirez. “Moreover, we knew this was specific to the memory of the blue box because if we placed the animals in any other box, they did not show fear behavior at all. A specific false memory had been formed and recalled.”

We are a long way, of course, from a sci-fi, mind control future in which false memories can be similarly introduced into a human brain, and for now at least, our recollection of things that never happened will continue to be formed in subtler and more natural ways. But the same dynamic—one memory circuit crosswiring to another—is at work in both cases. It’s the hallucinatory power of those memories that makes them seem so real, and it’s the sloppy way even so sophisticated organ as the brain operates that makes them possible in the first place.

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