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Brain-Hacking Scientists Turned Mice's Bad Memories into Good Ones

The emotional "valence" of a memory can be easily switched, once you know where in the brain it's stored.
Shocks produce bad memories, hanging out with female mice produces good ones. Image: Collective Next and Roger Redondo

Memories, generally speaking, can be good, bad, or neutral. And now, they can be changed from good to bad, and vice versa, from within the brain—in genetically engineered mice, at least.

Researchers at MIT have discovered which parts of the brain store the "emotional" part of a memory, and, in their latest study, published in Nature, were able to flip the emotional valence of a memory using light that targets specific neurons within the brain.

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To do this, they used a method known as optogenetics, in which modified neurons can be manipulated with light. In this study, the mice's brains were genetically modified so that when a certain antibiotic was removed from their diet, a light-sensitive protein was expressed in the brain, which allowed the researchers to watch memories being formed in the amygdala and the hippocampus.

A schematic of where the blue light was directed. Image: Redondo et. al.

The mice can then be forced to recall those memories with a blue light that's rigged directly to the neurons where those memories are held: Blue light on, memory on; blue light off, memory off.

One group of mice was given a small electric shock, which created a bad memory. The other group of male mice got to hang out with female mice, which created a good memory. They tossed the mice in a box divided into two sections, one normal and one that turned on the blue, memory-triggering light.

Unsurprisingly, shocked mice didn't spend much time in the section in which the memory was activated, while the other group, with pleasurable memories, did. From there, the researchers took the mice and put them in the opposite situation: Previously shocked mice hung out with female mice; male mice who hung out with female mice previously got shocked this time around.

The only difference was, this time, the blue light was activated, meaning they were actually "experiencing" the first memory again and not forming a new one. After that, the original memory's emotional value was found to be completely switched.

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POST-TRAUMATIC STRESS DISORDER COULD PROBABLY BECOME A THING OF THE PAST

"In the brain, there exists two competing neurocircuits—one involved in negative memories, and one involved in positive memories," Susumu Tonegawa, one of the researchers, said in a conference call with media. "We found that the competition of these circuits dictate the overall emotional value … and that we can switch a mouse's memory valence from negative to positive and from positive to negative."

In an accompanying paper analyzing the findings, Tomonori Takeuchi and Richard Morris of the University of Edinburgh wrote that "light is used to selectively reactivate the representation of the 'where' component of a memory and then change its 'what' association."

In other words, as Tonegawa explained, you could take a person who has been mugged in a dark alley and, without returning them to the alley or recreating the experience at all, can reprogram the way they feel about that experience.

The implications of this for treatment of psychiatric disorders, if it can be recreated in humans, are obviously enormous: Post-traumatic stress disorder could probably become a thing of the past, and therapy like this could potentially be used to treat several different types of anxiety. And that's where this is headed.

Memory modification is at the heart of other attempts to help treat PTSD and other similar afflictions, including the use of virtual reality or MDMA. But this research shows the potential for a more direct method, even if it's a ways from being used on humans.

Regardless, both Tonegawa and his coauthor, Roger Redondo, mentioned that they hope to use this research as the basis for new therapeutic treatments in humans.

"Now we can go inside the brain and change the way the mice reacts to a memory being brought back to mind without any drugs," Redondo said. "This memory manipulation occurs without the mice ever being brought back to the place where it happened initially, and all the manipulation is done from within the brain. This could be a novel avenue for therapies in the future."