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It’s possible to link and then unlink two unrelated memories in mice

This could one day help us eliminate PTSD triggers

Traumatic flashbacks that occur years after the event are one of the most painful parts of PTSD. They happen because the brain learned to associate the event with a separate memory that then becomes a trigger. A new study suggests that it’s possible to break the link between these two memories, at least in mice, and that further research could one day help us do the same for humans.

For the study published today in the journal Science, scientists taught mice to be afraid of two different things over time: a sugar solution that made them sick if they drank it, and a tone that was accompanied by a shock every time they heard it. Then, they taught the mice to associate the two fears with each other, says lead researcher Kaoru Inokuchi, a neuroscientist at the University of Toyama in Japan. This is important because we hadn’t known before whether this was possible. Finally, they destroyed the link between the two memories and found that the original memories remained intact. “In principle, we should be able to apply this approach to specifically dissociate a daily memory and also the traumatic event without affecting the individual memory,” says Inokuchi. This last part is important because it might be harmful to PTSD patients if breaking the link between a trigger (like the smell of lavender) and a painful event erased the original memories completely.

The first step was teaching mice to be afraid of both the taste and the sound. Each time the mice drank a sugar solution, the researchers injected them with chemicals that made them nauseated; the mice learned to associate the solution with nausea. They also made mice afraid of a certain tone by playing it while they were being shocked. The mice froze whenever they heard the tone.

Next, the scientists taught the mice to associate the fear of the sugar solution with fear of the tone. So, the animals heard the tone while drinking the sugar solution. Afterward, whenever they drank the sugar solution, they would freeze as well, expecting the shock, even when there was no tone.

We already know that if two unrelated events happen within a span of about six hours, those memories can get linked, says Thomas Rogerson, a neuroscientist at Stanford University who was not part of the study. So if you’re eating chocolate ice cream while getting dumped, chocolate ice cream might be ruined because it later reminds you of being told “it’s not you, it’s me.” But because Inokuchi’s team taught the mice the two fears over time, today’s study shows that you can also link mostly unrelated memories, as long as you make people remember them at the same time. “The actual memories don’t have to happen simultaneously or within a short amount of time,” says Rogerson. “The ability to connect disparate bits of information is no longer linked to them physically happening within the same few hours.”

Finally, the researchers identified the neurons that made up the two original memories, plus the neurons were the link between them. Then, they used a technique called optogenetics to erase the overlapping part. (In optogenetics, you use light to turn on or turn off certain neurons.) The mice no longer froze while drinking the sugar solution, but they were still separately afraid of the solution and the tone, just like before.

This is an exciting step forward for understanding how memories can be manipulated, but Inokuchi acknowledges that there are limits to application. For one, scientists need to insert an optic fiber cable in the brain to use optogenetic techniques. This can be tricky, or possibly risky, in humans. “But maybe in the future we will be able to develop a new technology in which we can manipulate activity from outside the brain, maybe through magnetic manipulation,” he says. “I am very optimistic.”