In the hippocampus, distinct neuronal cell-types interact together by selective synaptic contacts and neural activity patterns. Neuronal diversity is a hallmark of cortical networks. Systems Neuroscience Group, Institute of Physiology, University of Bern It was funded by the University of Bern, the Swiss National Science Foundation and the European Research Council (ERC). This study was carried out in partnership with the University of Bern, the Friedrich Miescher Institute and international collaborators. 'However, further studies are necessary to investigate whether discoveries obtained in simple animal models can be extrapolated to human anxiety disorders,' Ciocchi adds. A better understanding of these processes will help develop more specific therapies for these disorders. 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.

Important for developing more effective therapies 'The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear.' 'We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses,' says Ciocchi, Assistant Professor at the Institute of Physiology, University of Bern. This impaired the suppression of fear responses, whereupon animals became excessively fearful. For their study, the researchers used several methods, including a technique called optogenetics 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. They were able to identify different cell types that influence the animals' behaviour. The researchers led by Stephane Ciocchi and Andreas Luthi studied the activity of neurons of the central amygdala in mice during the suppression of fear responses. 'Disturbed' suppression leads to long-lasting fear These results were published in the journal Nature Communications. This shows that neurons in the central amygdala are highly adaptive and essential for suppressing fear. However, when they are activated, behaviour returns to normal despite previous fear responses. In animal models, it has been shown that inhibition of these microcircuits leads to long-lasting fear behaviour. Now, a group led by Professors Stephane Ciocchi of the University of Bern 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 fear responses, but it contains neuronal microcircuits that regulate the suppression of fear responses. This causes the body to release stress hormones, change heart rate or trigger fight, flight or freezing responses. The amygdala is a small almond-shaped brain structure in the center of the brain that receives information about fearful stimuli and transmits it to other brain regions to generate fear responses. Recent studies have shown that certain groups of neurons in the amygdala are crucial for the regulation of fear responses.

If this system is disturbed, for example if fear reactions are no longer suppressed, this can lead to anxiety disorders. A kind of 'tug-of-war' takes place, with one brain circuit 'winning' and overriding the other, depending on the context.

Different circuits of nerve cells are involved in this process. What was known so far is that distinct nerve cells interact together to regulate fear responses by promoting or suppressing them.

Normal fear vs pathological fear