The ability to rapidly detect a threat has tremendous survival value. For certain types of threats, such as natural predators, this ability is passed from one generation to the next. However, the ability to detect most threats is learned through the animal’s own life experience. Whereas processing an innate threat relies on a prewired circuit, learning a threat is implemented through synaptic plasticity; both, however, are processed in the basolateral amygdala (BLA). This raises the possibility that learning new threats recruits a prewired circuit in the BLA that evolved to process innate threats. To test this, we examined three key components within the BLA in mice—excitatory neurons, inhibitory neurons, and neuromodulators—during exposure to an innate visual threat (looming shadow) and a learned threat.

Single-cell-resolution imaging of excitatory neurons revealed that learning-induced plasticity was selectively expressed in neurons originally activated by the innate threat. This suggests that the neurons processing an innate threat are recruited for the representation of the learned threat.

Bulk calcium imaging from inhibitory neurons showed that the looming shadow activated VIP interneurons while suppressing SST. This suggests that the looming-induced defensive responses were triggered through disinhibition of the principal neurons. During threat conditioning, VIP and SST interneurons again exhibited distinct but complementary dynamics, suggesting that the same inhibitory motif is recruited during threat learning. Finally, we found that innate and learned aversive stimuli—but not a neutral stimulus—triggered the immediate release of norepinephrine (NE) in the amygdala. This suggests that NE lowers the activation threshold of the neurons processing both innate and learned threats. 

Together, our data support the hypothesis that threat learning recruits the prewired circuit processing innate threats.

More information:

• https://mbg.au.dk/en/research/research-areas/neurobiology/sadegh-nabavi