Decoding the brain mechanism in response to danger
A team of scientists from Neurocentre Magendie has discovered the brain mechanism involved in the response to danger. Recently published in the journal Nature, the study opens new leads for the treatment of patients suffering from anxiety disorders.
When faced with immediate danger, humans and animals share an avoidance mechanism which triggers the ability to flee for protection. In certain human subjects, this defense response is disproportionate, occurs outside of a context of danger, and is symptomatic of an anxiety disorder. Knowledge of the cerebral mechanisms responsible for this reaction is crucial to the development of long-term, effective treatment for patients suffering from such disorders.
There are two main defense reactions; immobility when danger is remote and avoidance when it is immediate. While the mechanisms of the first response are well understood by scientists, (it is easier to observe neuronal changes in an immobile animal), those of the second response remain obscure. In the last ten years, scientists were aware that two regions of the brain, the basolateral amygdala and dorsomedial prefrontal cortex, are involved, but they had yet to understand how these structures work together to trigger the avoidance response.
The key role of the amygdala and prefrontal cortex
Cyril Herry, an INSERM researcher at Neurocentre Magendie (INSERM and University of Bordeaux - Bordeaux Neurocampus), and his team observed the underlying neuronal mechanisms triggering avoidance in mice. The researchers placed the mice in a labyrinth consisting of two compartments. In one compartment, an unpleasant sound associated with a threat was emitted. The mice had the possibility to flee to the second compartment, thus stopping the sound associated with danger.
In order to understand the role of the amygdala and prefrontal cortex in this avoidance strategy, the researchers temporarily inhibited one of these two regions in the mice subjects during the experiment. They then used optogenetic* methods combined with recordings of neuronal electrical activity, enabling them to manipulate and observe in real time the behavioral changes produced on a neuronal level. The results were remarkable; when the mouse receives the auditory stimulus, the avoidance mechanism is severely disrupted, regardless of the inhibited region (amygdala or prefrontal cortex). This demonstrates the key role of these two brain regions, both in the recognition of danger and the avoidance response.
Furthermore, the scientists discovered that the prefrontal cortex not only associates the sound with a threat, it also controls the ensuing action. In the second prior to the mouse making the decision to flee, the researchers observed an activation of the neurons in the prefrontal cortex. The amygdala then intervenes to maintain this association between the unpleasant sound and decision to flee in the animal’s prefrontal cortex. The persistence of this information in the prefrontal cortex, thanks to the amygdala, is what ultimately enables the animal to make the decision to flee. The avoidance mechanism is thus conditioned by the interaction between the amygdala and the prefrontal cortex.
A promising breakthrough in the treatment of anxiety disorders thanks to A.I.
Artificial intelligence enables us to predict animal behavior, based on past neuronal activity patterns. This technique has seldom been applied, however, to research linked to emotional behavior.
In this study, AI was used to predict the animal’s behavior in the presence of danger, a technique which is fully applicable in human subjects. While this method has yet to be tested in humans, “with artificial intelligence, it would be possible, depending on a recording in real time of brain activity, to predict the behavior of an individual in a negative emotional situation, and potentially to develop tools to regulate in real time the associated neuronal changes”, Cyril Herry, co-author of the study, points out.
This is a significant advance for patients suffering from post-traumatic stress disorder or generalized anxiety who demonstrate an excessive avoidance response in the absence of any real danger. The ability to predict neuronal changes associated with this anxiety will enable the treatment of symptoms in real time and to target the underlying physiological causes.
*Optogenetics consists in genetically modifying certain brain cells to render them sensitive to light. This in turn enables, for example, certain closely-targeted neurons to be activated or inhibited thanks to light rays, without affecting surrounding neurons. This technique thus helps to explore the cause-effect links between neuronal activities and behavioral manifestations.
Jercog, D., Winke, N., Sung, K. et al. Dynamical prefrontal population coding during defensive behaviours.
Researcher at Neurocentre Magendie