Serotonin Neuron Activity Patterns Support Cognitive Flexibility


Serotonin is a molecule that plays various roles in the human body. In the brain, it is involved in regulating mood and emotions.

Growing evidence suggests that serotonin also helps animals, including humans, adapt their behavior to changes in their environment. To allow for such behavioral flexibility, serotonin might promote changes in the underlying brain structures and activity.

In a type of learning known as ‘reversal learning’, for instance, it is necessary to adapt to a sudden change in a previously familiar environment. For example, if there were a road closure on a person’s way to work, they might want to learn to stop following their usual route and learn a new and better one.

Previous research has shown that when serotonin signaling is reduced, people persevere. That is, they will keep following the old route even if it is no longer the best choice. How this process works is still largely unknown.

Neural And Behavioral Flexibility Molecule

To start unraveling these mechanisms, Sara Matias and her colleagues at the Champalimaud Centre for the Unknown, in Lisbon, trained mice in a reversal learning task while manipulating and recording the activity of the neurons in the raphe nuclei that produce serotonin.

The results showed that when the activity in serotonin neurons was experimentally blocked, the mice tended to keep looking for a reward that was no longer available. Then, by recording the activity of serotonin neurons, Matias et al. found that it was the surprise of discovering a change in a previously familiar environment that activates serotonin neurons.

It did not matter whether the change was better or worse than expected. The findings suggest that together with dopamine, another molecule involved in learning from rewards, serotonin could play an important role during reversal learning.

One next step will be to determine if serotonin mainly stops perseverance in its tracks, or whether it works by helping to unlearn the old behavior, or a combination of both. In the future, this could further our understanding of depression, which can be viewed as a mood disorder characterized by patients being unable to adapt to adverse situations, leaving them trapped to repeat behaviors and thoughts that are not beneficial.

Future studies could also build on these findings to guide the development of new treatments for depression that involve serotonin. Sara Matias, speaking to the Champalimaud Foundation’s AR Magazine, said:

“We think serotonin is not the happiness molecule. It is the neural and behavioral flexibility molecule. It gives us the opportunity to change, but we still have to do something for that change to go in a positive direction. Maybe that’s why SSRIs work much better when combined with behavioral psychotherapies than when used alone.”

The work was supported by the Fundação para a Ciência e Tecnologia, Human Frontier Science Program, European Research Council and Champalimaud Foundation.

  1. Sara Matias Eran Lottem Guillaume P Dugué Zachary F Mainen. Activity patterns of serotonin neurons underlying cognitive flexibility. eLife 2017;6:e20552

Last Updated on November 18, 2023