A team of scientists has managed to transform negative memories into positive ones by artificially activating neural circuits in the brain of mice
First, they generated bad memories associated with a place in the mice, and then the pleasant ones returned – or vice versa – without the need to return to the place in question.
The neurons that housed the memory of the place were reactivated in a different emotional context, thus modifying the association.
As the researchers point out, the work, published by the scientific journal Natureoffers the possibility of better understanding how emotional memory forms and changes.
A place, a memory, a fear
«Emotion is intimately associated with memories of past events and episodes, but ‘valence’ – the attractiveness or aversion of memories – is malleable,» said Susumu Tonegawa, a researcher at the Riken-MIT Center for Neural Circuit Genetics. in Massachusetts , USA, and author of the study.
Tonegawa gave as examples a mugging or a happy vacation: experiences that can make a subject walk down a particular street or have a special predilection for a beach.
We all know that these kinds of emotional associations can change with a new experience. For example, memories of a favorite beach can turn sour with news of a shark attack.
Therapists today use this malleability to treat trauma victims or people with depression, trying to replace negative associations with positive ones.
But Tonegawa and his team have managed to pinpoint some of the connections that make this happen inside the brain.
Two years ago, the scientists showed that they could tag the cells that harbor a new fearful memory in the brain of a mouse and activate them again at another time to elicit fearful behavior.
Then, in 2013, they tagged the memory of a location and then activated it while giving the mice mild electric shocks. This created a false fear association with the original site.
Now they have managed to change the emotional content – happy or fearful – of a memory from one extreme to the other.
The power of a blue light
In their experiment, the researchers induced male mice to have negative experiences consisting of electric shocks in a particular room and marked the neurons involved in that memory with «optogenetics.»
This technique installs a kind of switch in those neurons through genes that make the cells sensitive to light. Then, a beam of blue light, sent into the brain via fiber optics, allows those neurons to be turned on or off at will.
In the laboratory and the day after the creation of the bad memory, with the mice in a different room, the scientists stimulated the marked neurons with blue light and effectively «reactivated» the original fearful memory.
At this point the mice were given the option of leaving the light on or off, and they preferred to turn it off.
But then the scientists stimulated the tagged neurons at the same time they gave the mice a positive emotional signal (the company of a female), in an attempt to change the emotional association of the memory.
And again they gave the mice the choice: leave the blue light off or on. This time, they wanted it on.
The original memory trace had been altered, and now they liked it.
And as an important detail, once they returned to the first room, in the absence of any brain stimulation, the mice were less fearful than after the first round of training: their memory of the place had changed for the better.
The procedure also works in reverse, and scientists can cause the change from an original positive memory to a negative one.
In addition, by installing optogenetic switches in different parts of the brain, researchers will be able to identify that changes in memory occur through delineations in the connections between the hippocampus, which houses spatial information, and the amygdala, which drives the response. emotional.
Experts believe that a spatial memory, housed in brain cells in the hippocampus, can «call» different groups of neurons in the amygdala, invoking positive or negative emotions.
His experiments altered those connections so that the original memory triggered another emotional response.
«We can change the way mice react to a memory without using drugs,» said Roger Redondo, another of the study’s authors.
«This occurs without the mouse going back to the original place where the memory was formed. All the manipulation is done from within the brain.»
men and mice
It’s hard to know, however, whether the artificial recalls, powered by beams of blue light inside a mouse’s brain, are similar to memories as we know them.
«We can’t ask the mouse what it’s thinking,» said Richard Morris, a memory expert at the University of Edinburgh, UK, who was not part of this research.
«All we can do is ask the mouse: if I turn on this light, how are you going to behave in relation to what it evokes?»
Tonegawa, for his part, points to the consistent behavior observed in his experiments.
«The mice were obviously expressing the consequences of the memory in their behavior, therefore we assume that they have the sensation of the memory.»
But scientists are cautious about the human application of their discoveries. They assure that it is unlikely that the advance can be applied in humans with traumatic memories.
«It may take several years of work, but you never know,» Redondo said. «Technology is moving faster and these optogenic tools keep advancing.»
But according to Morris the study is valuable for other reasons.
«No one is going to line up to have light guides inserted into their brains and to be shown blue light,» the expert told the BBC.
«But these results help us understand the proportion of cells involved when you have to change a negative memory into a positive one. Are we talking about changing 50% of the cells in the amygdala, just 1%, or even less?» .
«I think it’s important to move beyond behavioral understanding and have a deeper understanding of the clinical task at hand.»