Anna Beyeler Understanding anxiety pathways to control it better

We're not all equal when it comes to anxiety

Anxiety disorder is when a person feels strong, long-lasting anxiety that disrupts daily life but is not related to any real danger or threat. There are many risk factors, including childhood physical and/or emotional trauma, linked to developing this disorder. However, the neurobiology behind the risk of developing anxiety remains a mystery. As a result, available treatments are limited and have side effects as their mode of action is not yet fully understood. The most often used treatments target the cerebral serotonergic system, which produces the neurotransmitter serotonin and distributes it to many areas of the brain, where it regulates the activity of neurons. It is a key, very powerful system to maintain the balance of brain functions, including anxiety control.

Serotonin: a suspect to keep an eye on

Failures in serotonergic transmission in several parts of the brain have been observed in patients with anxiety disorders. These clinical observations suggest a link between serotonin and anxiety, but Anna Beyeler wants to find iron-clad proof. 

With her team at Neurocentre Magendie, she is focusing on the brain's main source of serotonin, the dorsal raphe nucleus, and the areas that receive it, including the limbic circuits that control emotions. Cutting-edge neuroscience technologies will enable researchers to understand the contribution of serotonin and limbic circuits to anxiety disorders in mice.

Understanding the neural circuits of anxiety

To carry out this project funded by Impulscience^®, the team will develop a robust procedure for assessing anxiety in rodents. They will combine physiological measurements (heart rate, temperature, shivering) with analysis of anxiety-like behaviour. These behaviours are quantified by multiple measurements including time spent in protected versus exposed locations, and fine-tuned measurements of behaviour detected using an artificial intelligence algorithm. With unprecedented resolution, the researchers will identify the signs of low or high anxiety in mice, allowing them to take each individual’s variability and vulnerability into account.

These new approaches will provide answers to many fundamental questions, including: 

• Are serotonergic circuits the same in resilient and anxiety-prone individuals? 
• How can a risk factor like early-life stress change brain circuits? 
• Can physiological anxiety levels in vulnerable individuals be restored by manipulating serotonergic circuits? 

This vast program will offer a new understanding of the factors controlling anxiety levels between individuals while providing hope for finding out how therapies targeting the serotonin system work in the treatment of anxiety disorders.