Central amygdala microcircuits mediating learning and expression of passive and active defensive behaviours

The survival of all living beings is dependent on their ability to detect and adapt to environmental changes. Especially in the face of threat, the modus operandi needs to be adjusted in order to minimise potential harm and increase the likelihood of survival. Animals not only adapt their physiology, but also their behaviour. A large body of evidence shows that amygdala is a region of the brain crucially involved in innate and learned defensive behaviours. Its role in encoding passive defensive reactions elicited by classical fear conditioning has been thoroughly studied both on molecular and circuit levels. However, not much is known about amygdala circuits involved in active defense, such as flight.
Here, the role of central amygdala protein kinase C - delta (PKCδ+) and somatostatin (SOM+) expressing neurons in both defensive freezing and flight was explored with the help of a two-way active avoidance conditioning paradigm. Optogenetic activation of PKCδ+ neurons resulted in boosted learning and expression of active avoidance. In contrast, activation of SOM+ neurons had the opposite effect on behaviour. Additionally, calcium imaging of PKCδ+ neurons showed that a sizeable fraction of this population changes its activity to conditioned stimuli during active avoidance learning.
Using optogenetics and imaging, we thus confirm that the central amygdala mediates active defensive behaviours. Furthermore, we specifically identify that PKCδ+ neurons not only regulate passive, but also active defensive behaviours. PKCδ+ neurons are thus in a position of power, which allows them to influence very different defensive strategies acutely and flexibly. Additionally, they also optimise adaptation to threatening situations in the long run via their lasting effects on learning.