Anna Beyeler Explores the Circuits of Anxiety

Little is known about the biological origin of anxiety and particularly that of pathological anxiety, which affects almost 20% of the population. But thanks to the Atip-Avenir team that she founded two years ago and has been the leader of ever since, Anna Beyeler, Inserm researcher at Neurocentre Magendie in Bordeaux, has challenged herself to elucidate some of the mechanisms of this psychiatric disorder.

Anna Beyeler
Anna Beyeler

Anxiety – particularly the neurobiological dysfunctions behind its pathological forms: this is what Anna Beyeler, leader of the Neural Circuits of Anxiety team at Neurocentre Magendie*, has chosen to tackle. Anxiety is first and foremost a natural phenomenon, a transient adaptive response to confront an ordeal or anticipate danger. But when it becomes excessive, sustained, and occurs outside of an anxiogenic context, it is considered pathological. However, despite being the most common psychiatric disorder, affecting almost 20% of the population, not a lot is known about its mechanisms.

The insular cortex as target

Beyeler’s hypothesis is that in pathological anxiety, the neural circuits that control this physiological reaction are disrupted. In particular, she supposes an alteration of the circuits responsible for attributing positive or negative values to the various stimuli that surround us: the emotional valence circuits. This hypothesis would explain why exposures to certain products, situations or sensations trigger abnormal reactions. "This has not yet been tested biologically and is something we would like to verify", she explains. To do this, she intends to focus on a specific region of the brain: the insular cortex. According to a number of functional imaging studies, this region plays a role in anxiety disorders. It is also implicated in emotional valence, particularly that of taste, touch, and pain sensations.

Although the final aim is to understand pathological anxiety in humans, the researcher is currently studying mice. "In these animals, we have contributed to the development of techniques to analyze the activity of groups of one hundred neurons that are referred to as 'neural populations'. We are unable to achieve this level of precision in humans. In our study model, we can also activate or decrease the activity of a neural population and observe how this impacts behavior", she continues. Thanks to these analyses, and also by studying the neurotransmitters released or the genetic expression profile of the cells concerned, Beyeler and her team hope to gradually reveal the secrets of the functional abnormalities behind pathological anxiety.

A long-standing passion

In fact, Beyeler is realizing a dream that dates back to 2005. "During a master’s internship, I had the opportunity to record the electrical activity of neurons and study their functional role. It was a revelation", she recalls. It was then that she decided to specialize in electrophysiology and gave herself the means to do so. Her PhD focused on spinal cord circuits and her post-doc, in Bordeaux, on brain oscillations – variations that reflect the transmission of neural information. Two years later, she obtained a second post-doc, this time at the Massachusetts Institute of Technology in Cambridge, USA. There she spent five years studying the circuits of emotional valence and anxiety in the amygdala, a different brain region which until then had been studied more than the insular cortex

She returned to France in 2017, joining Neurocentre Magendie thanks to a "Chaire d’Accueil" grant from Université de Bordeaux. One year later, she obtained Atip-Avenir funding to create her own team within the same laboratory, and in 2020 she joined Inserm as a staff scientist. Her team now includes two doctoral students, two post-docs, and has already trained ten master’s students. Her Atip-Avenir funding, initially for three years, could be extended by two years depending on her findings, which she hopes will soon be robust!

*Unit 1215 Inserm/Université de Bordeaux, Neurocentre Magendie, Bordeaux