Does the thought of your first kiss still bring you goose bumps or does the memory of a traumatic experience still give you the same rush of anxiety that you experienced before? That’s because the brain pathway that links external events to an internal emotional state involves different parts of the brain to form a single memory. This was demonstrated by researchers from the RIKEN-MIT Center for Neural Circuit Genetics, who also showed that positive or negative emotional valence of memory can be reversed during later memory recall.

The study, published in Nature, was conducted by Dr. Susumu Tonegawa and his team. They wanted to know how brain regions like the hippocampus and amygdala were involved in forming memories and if the emotional valence was stored in the same part of the brain as the memory of an event that caused the emotion. Valence is a psychological term used to describe the intrinsic attractiveness (positive valence) or averseness (negative valence) in response to an event or object.

"Both the hippocampus and the amygdala are considered critical for memory formation. We wanted to know whether the memory engram was free to associate with positive or negative valences or whether it was fixed with respect to emotion," said Roger Redondo, who along with Joshua Kim is co-first author of this study, in a press release. "We also wanted to know at what point in the circuit the valence is assigned to the engram, in the hippocampus or the amygdala." 

The experiments were conducted on mice. They were placed in a novel chamber and divided into two groups. One group received mild shock on their foot while the other group was allowed to socialize with a female mouse. So the mice formed memories of fear and pleasure. Using biomarkers, the scientists genetically labeled neurons that were active during the formation of either memory.

The team then used optogenetics to activate the same set of neurons. Optogenetics uses light sensitive microbial ion channels to manipulate neural activity. The activated neuron can be controled using light delivered by an LED or laser.

When the neurons were activated, the mice showed the same response as they did when they experienced the event. In other words, depending on the valence of the initial experience, the researchers could judge from the mouse's behavior whether the activated memory was a fearful one or a rewarding one, displayed by the mice when they avoided or were attracted to a particular location in the chamber.

"If our technology drives memory engrams, it should work independently of whether the valence is negative or positive," Redondo explained. "We wanted to show that the memory reactivation was not restricted to fear memories, as we had used in the past." 

Next, the team wanted to find which part of the brain stored memory of an event and its emotional valence. For this, they had to switch the valence of memories in mice from negative to positive and vice versa. To do this, the mice were given a new experience of the opposite valence while the researchers simultaneously activated the original memory in either the hippocampus or the amygdala.

As a result, the memory engram stored in the hippocampus could change its valence. So the mice who had earlier received foot shocks were no longer fearful when recalling that experience, while mice that originally socialized with a female now showed fear. The valence of the memory engram in the amygdala, on the other hand, could not be altered.

With this, the researchers concluded that memories of either emotion can be reversed in the hippocampus. But the amygdala carries only positive or negative memory and cannot interchange. This study reveals an unanticipated flexibility in brain circuits during memory formation for emotional events.

This research could be a stepping stone to develop psychological interventions in people suffering from depression or post-traumatic stress disorder, where negative emotional valence can be reversed to positive valence.