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Because they can be used to treat anxiety disorders, the brain mechanisms that suppress fear reactions have been a focus of much attention. Although we have a good understanding of the brain regions that are activated when fear is experienced, it remains to be largely unknown how fear reactions can be suppressed. Researchers from the University of Bern, and the Friedrich Miescher Institute of Basel discovered that fear responses can be suppressed by activating central amygdala neurons.
Fear is an important response that protects us from danger. Anxiety disorders and persistent fears can result from anxiety disorders that are uncontrollable fear responses. Around 15% of Europe’s population suffers from anxiety disorders. Because of a lack of neurobiological knowledge, existing therapies are often not specific or effective.
It was discovered that different nerve cells work together to regulate fear reactions by either promoting or suppressing them. This process involves different circuits of nerve cell. This is a “tug of war” in which one brain circuit wins and the other loses depending on the context. Anxiety disorders can develop if this system is disrupted. For example, if fear reactions no longer are suppressed.
Recent research has shown that certain neurons in the amygdala play a crucial role in controlling fear responses. The amygdala, a small brain structure with almond-shaped shape in the middle of the brain, receives fearful stimuli information and relays it to other brain areas to create fear responses. This triggers the body to release stress hormones and alter heart rate.
A group of researchers led by Professors Stephane Ciocchi of University of Bern, and Andreas Luthi of Friedrich Miescher Institute Basel, has now discovered that the amygdala is a key component of these processes. Not only is it a “hub” for fear responses, but also contains neuronal microcircuits which regulate fear suppression. It has been demonstrated that these microcircuits can be inhibited in animal models. This results in long-lasting fear behavior. However, if they are activated, the behaviour of animals returns to normal, despite previous fear responses. This indicates that the central amygdala neurons are adaptive and necessary for suppressing fear. These findings were published in the Nature Communications journal.
Long-lasting fear is caused by “disturbed” suppression Stephane Ciocchi, Andreas Luthi and others studied the activity in the central amygdala neurons during suppression of fear responses in mice. They were able identify the cell types that affect animals’ behavior. The researchers used a variety of methods to study the matter. One method was optogenetics, which allowed them to precisely stop – using pulses of light- a neuronal population in the central amygdala responsible for a specific enzyme. The suppression of fear response was impaired, and animals became extremely fearful.
We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses. The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear.”
Stephane Ciocchi, Assistant Professor, Institute of Physiology, University of Bern
It is crucial for the development of more effective therapies Humans may experience fear memories that are not suppressed due to dysfunction in this system. This could include deficient plasticity in central amygdala nerve cells. These processes can be better understood to help develop specific treatments for these disorders. Ciocchi says that further research is needed to determine if findings from simple animal models can be applied to anxiety disorders in humans.
The University of Bern, Friedrich Miescher Institute, and other international collaborators collaborated in this study. The University of Bern, Swiss National Science Foundation, and European Research Council (ERC) funded it.
Systems Neuroscience Group, Institute of Physiology University of Bern Cortical networks are marked by neuronal diversity. Different neuronal cell types interact with each other in the hippocampus through selective synaptic contacts, neural activity patterns, and different neuronal cell-types. We study how different emotional and cognitive behaviors emerge in complex neuronal circuits within the ventral CA1 (hippocampus) brain region. This is a brain area that is crucial for context-specific emotional memories and anxiety, as well as goal-directed actions. The selective recruitment of large- and micro-scale neural circuits in the ventral CA1 (hippocampus) is what we believe will lead to distinct behavioural programs. We combine single-unit recordings from ventral CA1 GABAergic internurons and projection neurons, selective optogenetic strategies and cell-type-specific viral tracing to identify the circuit motifs. Our experimental methods will reveal fundamental neural computations that underlie learning and memory in higher cortical brain areas.
University of Bern
Whittle, N., et al. (2021) Central amygdala micro-circuits mediate fear extinction. Nature Communications. doi.org/10.1038/s41467-021-24068-x.