Fear is an important reaction that warns and protect us from danger but when fear responses are out of control, this can lead to persistent fear and anxiety disorders. In Europe, about 15 percent of the population is affected by anxiety disorders and many other countries. Existing therapies remain largely unspecific or are not generally effective because the detailed neurobiological understanding of these disorders is lacking.
What was known so far is that distinct nerve cells interact together to regulate fear response by promoting or suppressing them. Different circuits of nerve cells are involved in this process. A kind of “tug-of-war” takes place, with one brain circuits “wining” and overriding the other, depending on the context. If the system is disturbed, for example, if fear reactions are no longer suppressed, this can lead to anxiety disorder.
Recent studies have shown that certain groups of neurons in the amygdala are crucial for the regulation of fear responses. The amygdala is a small almond-shaped brain structure in the centre of the brain that received information about fearful stimuli and transmits it to other brain regions to generate a fear response. This causes the body to release stress hormones, change heart rate or trigger fight, flight or freeze response.
Now a group led by Professor Stephanie Ciocchi of the University Been and Andreas Luthi of the Friedrich Miescher Institute in Basel has discovered that the amygdala plays a much more active role in these processes than previously thought: Not only is the Central amygdala a “hub” to generate a fear response, but it contains a neuronal micro-circuit that regulates the suppression of fear responses. In animal models, it has been shown that inhibitor of these micro-circuits leads to long-lasting fear behaviour. However, when they are activated, behaviour returns to normal despite previous fear responses. This shows that neurons in the central amygdala are highly adaptive and essential for suppressing fear. These results were published in the journal Nature Communication.
The researchers led by Stephanie Ciocchi and Andreas Luthi studies the activity of neurons of the central amygdala in mice during the suppression of fear responses. They were able to identify different cells type that influences the animal behaviour. For their study, the researchers used several methods, including a technique called optogenetic with which they could precisely shut down- with pulses of light- the activity of an identified neuronal population within the central amygdala that produces a specific enzyme. This impaired the suppression of fear responses, whereupon animals became excessively fearful. “We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses”, says Ciocchi. “The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear”.
In humans, dysfunction of this system, including deficient plasticity in the nerve cells of the central amygdala described here, could contribute to the impaired suppression of fear memories reported in patients with anxiety and trauma-related disorders. A better understanding of these processes will help develop more specific therapies for these disorders. “ However further studies are necessary to investigate whether discoveries obtained in simple animal models can be extrapolated to human anxiety disorders”, Ciocchi adds.
This study was carried out in partnership with the University of Bern, the Friedrich Miescher Institute and International Collaborators. It was founded by the University of Bern, the Swiss National Science Foundation and the European Research Council (ERC).