Donna Coveney / MIT

Scientists able to 'reverse' emotions associated with memories

In MIT study, neuroscientists changed the emotions linked to specific memories in mice

Erasing the anguish associated with a breakup or a traumatic event may soon no longer be confined to the realm of science fiction, or the central idea of the film “Eternal Sunshine of the Spotless Mind,” following an apparent breakthrough by scientists at the Massachusetts Institute of Technology.

Neuroscientists at MIT have honed in on the pathway of brain cells that appear to control the way our memories become linked to emotions — and have been able to “reverse” the emotion in mice linked to a specific memory, turning bad memories into good and vice versa. They published the results of their study in the journal Nature on Wednesday.

By targeting specific brain cells located in the hippocampus — the center of the brain that deals with the formation of memories — the scientists were able to “turn on” those positive and negative emotions. They did this by using a technique called optogenetics, which uses a light-sensitive protein to track specific brain cells, allowing them to be switched on and off when pulsed with light. 

Their experiment was done in mice, but the researchers say this circuit of brain cells could perhaps be a target for drugs that would treat post-traumatic stress disorder. In cognitive-behavioral therapy, the hope is that the fear and trauma associated with the memories of a painful event will gradually lessen the more a person talks about them. But isolating the area of the brain where the emotions are actually encoded with memory could greatly inform further research.

"Recalling a memory is not like playing a tape recorder," said Susumu Tonegawa, an MIT neuroscientist and a lead author of the study. "It's a creative process."

Tonegawa won the Nobel Prize for physiology or medicine in 1987 for his research on the immune system and antibodies. But in recent years, he has delved into the neuronal circuitry tied to learning and memory.

In 2003, he was able to isolate and alter the gene that regulates spatial memory in mice, causing confusion in laboratory mice that had ordinarily been able to learn how to run through complicated mazes. And last year he and a team of neuroscientists were able to implant a false memory in mice by manipulating specific cells in the brain’s hippocampus.

Because previous studies that have shown that our memories can be malleable, the team wondered if they might be able to change the emotions linked to those memories.

First, they created some good and bad memories in a group of mice, all male – some were allowed to cavort with female mice, and others were given a mild electric shock. Next, the scientists pulsed light on the mice’s brains to activate the same neurons used when they’d had those positive and negative experiences.

Perhaps not surprisingly, the mice that had socialized with females spent more time in the portion of the cage where they’d last experienced that pleasure, and the mice that had been shocked avoided that portion of the cage out of fear.

Then, the scientists wondered if they could reverse or lessen the feelings tied to those memories. While pulsing light on those memory-related neurons to switch them on, they gave electric shocks to the previously happy mice, and let the previously fearful mice socialize with females.

It turned out that the mice that had previously been shocked spent time on the side of the cage where it happened, associating it with pleasure – and the mice that had originally been rewarded with female company were now afraid of that side of the cage.

The neuroscientists had effectively been able to turn good feelings into bad ones, and vice versa, by activating the brain cells in the hippocampus where those memories were encoded.

When they ran the whole experiment again, but this time tracking brain cells in the amygdala — the part of the brain that processes emotions — they found they were once again able to induce pleasure or fear in mice. But this time they couldn't turn the pleasure and pain around. This, the scientists said, showed that the link between emotions associated with specific memories are found in the stretch of neurons that connect the hippocampus to the amygdala.

"In the future, one may be able to develop methods that help people to remember positive memories more strongly than negative ones," said Tonegawa.

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