Neuroscientists discover role of serotonin in resilience

Simply observing others cope with a traumatic experience can increase our resilience and prevent pathological states that can result from it, including depression. Neuroscientists at UNIL have demonstrated the presence of this “emotional contagion” in mice, and have managed to decipher its mechanism.

The neurotransmitter serotonin, released in a brain structure called the habenula, has been shown to be key to resilience. The discovery, published in Sciencerevisits the role of serotonin and opens new perspectives, particularly for the understanding of depression and its treatment.

Human beings have the ability to cope with unpleasant experiences and still live a normal life. This ability is known as resilience. However, some individuals are more vulnerable to traumatic events. They develop a loss of motivation and energy, which are characteristic of depression.

Promoting resilience in these at-risk individuals could help counter their vulnerability and constitute a preventive practice against the possible emergence of a pathological state. But there are still too many unknowns for resilience to be used as a preventive practice.

“There is a lack of clinical tools or underlying mechanisms to promote this type of conditioning capable of promoting a resilient response as in healthy people,” explains Manuel Mameli, associate professor in the Department of Basic Neurosciences at the Faculty of Biology and Medicine of the University of Lausanne (UNIL).

To achieve this, we need to understand the brain function behind adversity, a challenge that Mameli’s team has successfully addressed.

Observe to preserve yourself

To explore the underlying brain mechanisms, UNIL neuroscientists first designed an experimental model capable of promoting resilience and measuring its consequences on the appearance of pathological traits following trauma.

“We started from the observation that simply observing the emotional experiences of others helps us learn from them. This is a phenomenon known as emotional contagion, which calls upon resilience,” explains Mameli.

To achieve this, an “observer” mouse was placed near a mouse that was subjected to small electric shocks on its legs. This simple task protected the majority of the observer mice from developing pathological states of depression when they were themselves subsequently exposed to this unpleasant experience.

This was not the case for mice that had not witnessed their companions’ traumatic experiences. The scientists concluded that simply observing others cope with a traumatic experience increases an individual’s resilience and helps protect them against possible pathological consequences.

Serotonin, the molecule of resilience

Following the discovery of this behavioral principle, neuroscientists were able to identify the brain mechanism that governs it. They focused on the habenula, a tiny brain structure located in the heart of the brain, known to participate in emotional and sensory processing, and to regulate neurotransmitters associated with depression, including serotonin.

To achieve this, they specifically developed imaging tools to track this molecule in mice.

“It is very difficult to measure the variation of serotonin in the brain. Thanks to a biosensor developed by Yulong Li of Peking University, co-author of the study, we were able to identify the key mechanism,” adds Mameli.

Recordings made during behavioral experiments revealed that emotional contagion coincided with a lasting change in the functioning of habenula neurons, as well as an increase in the release of serotonin in this region.

More specifically, according to Sarah Mondoloni, a postdoctoral researcher in Mameli’s lab at UNIL and the study’s lead investigator, “it’s the dynamics of serotonin that change during this task, and that’s the key result of our study.”

By artificially altering the dynamics of serotonin levels, the research team was able to demonstrate that not increasing it not only compromises the lasting change in neuronal activity in the habenula, but also the ability of the mice to foster resilience after adversity.

Re-exploring the mechanisms of depression

A common denominator between the resilience mechanism after adversity discovered in this study and that of depression is serotonin. Many antidepressants target serotonin to increase its concentration in the brain. Here, neuroscientists show that a transient and localized increase in the habenula can prevent the onset of apathetic behavior following a traumatic experience.

“This property of the serotonin system is exciting information for neuroscientists. But our discovery could also open the way to new therapeutic applications relevant for depression, for example by testing existing pharmacological serotonin activators, including psychedelic therapies that stimulate the serotonin system. Their use could be refined to obtain better therapeutic approaches,” concludes Mameli.