Neural mechanisms for fear precision in the lateral amygdala

Abstract

The appropriate response to environmental stimuli is crucial for animal survival. Animals can discriminate safety cues from threatening stimuli to diminish fear generalization, one characteristic of anxiety disorders and stress-related disorders. Although fear generalization still exists when novel stimuli are similar to the conditioned stimulus (CS), mice can discriminate distinct stimuli. However, the neural mechanisms under precise fear responses are still unclear. Here, we show that after fear learning, engram cells in the lateral amygdala (LA) receive an enhancement of excitatory transmission specific to CS but not to novel cues. However, there is a general enhanced inhibition to engram neurons from both CS- and novel cue- inputs that causes a novel cue-induced biased inhibition. Suppression of Parvalbumin (PV) interneurons during fear memory retrieval attenuates fear discrimination between CS and novel cue through non-specific reactivation engram neurons, evidenced by artificial chemogenetic inhibition of PV interneurons in LA increases the amount of engram neurons that reactivated at retrieval test with novel cue. Our study provides a possible neural mechanism of fear precision that suppresses non-specific novel cue-induced activation of engram neurons by PV interneurons in LA.