Associating positive or negative emotions to specific memories is core to our survival, allowing us to avoid dangers or seek out beneficial things. Now, researchers at the Salk Institute have identified a specific molecule that seems to drive the assignment of emotion to memories, which could lead to new treatments for anxiety and depression.

Say for instance you ate something you found on the ground, then were horribly sick – you’d end up with negative emotions attached to that memory, and hopefully would learn not to eat floor food in the future. Inversely, the high you feel after a workout should encourage you to do it again.

This instinct has helped humans, and all life, survive over billions of years. In this context, a positive or negative emotion is called a valence and the brain’s ability to assign them to specific memories is known as valence assignment. Previous work by the Salk team traced valence assignment to a group of neurons in a brain region called the basolateral amygdala.

“We found these two pathways – analogous to railroad tracks – that were leading to positive and negative valence, but we still didn’t know what signal was acting as the switch operator to direct which track should be used at any given time,” said Kay Tye, senior author of the study.

For the new study, the researchers investigated what this signal may be. They examined some of the neurotransmitters produced by the associated neurons, and singled out one in particular called neurotensin.

In tests, the team used CRISPR to remove the gene for neurotensin in mice, and studied their ability to associate emotions to two different tones. One tone was followed by a sweet taste and the other a bitter taste, so ideally the mice should be able to learn to associate the first tone with a positive emotion and the second with a negative.

Intriguingly, mice that had no neurotensin signaling couldn’t learn to associate the first tone with the positive stimulus, but formed a stronger than usual association between the second tone and the negative stimulus. This, the team says, suggests that the brain defaults to negative valence until neurotensin switches an experience to positive valence. This fear bias could have deep evolutionary roots.

In later experiments the team tested the inverse by expressing more neurotensin in mice, and found that the animals exhibited higher reward learning and lower negative valence. In theory, this could hint at a possible mechanism for anxiety or depression, and a potential new way to treat them.

“We can actually manipulate this switch to turn on positive or negative learning,” said Hao Li, co-first author of the study. “Ultimately, we’d like to try to identify novel therapeutic targets for this pathway.”

The research was published in the journal Nature. The team discusses the work in the video below.

Making a memory positive or negative

Source: Salk Institute

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