The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a novel combination of chemogenetics, activity-based neuronal-ensemble labeling, and in vivo electrophysiology, we found that fear extinction learning confers parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) with a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6–12 Hz oscillation and a fear-associated 3–6 Hz oscillation within the BLA. Loss of this competition increases a 3–6 Hz oscillatory signature, with BLA→mPFC directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV-interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

Highlights d Acute activation of dorsal and ventral HPC engrams in mice drives reward and aversion d The ventral DG is preferentially reactivated in emotionally salient contexts d Chronic activation of HPC engrams decreases or increases context-specific freezing d Memory enhancement is disrupted when BLA cells processing fear are silenced

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The formation and extinction of fear memories represent two forms of learning that each engage the hippocampus and amygdala. How cell populations in these areas contribute to fear relapse, however, remains unclear. Here, we demonstrate that, in male mice, cells active during fear conditioning in the dentate gyrus of hippocampus exhibit decreased activity during extinction and are re-engaged after contextual fear relapse. In vivo calcium imaging reveals that relapse drives population dynamics in the basolateral amygdala to revert to a network state similar to the state present during fear conditioning. Finally, we find that optogenetic inactivation of neuronal ensembles active during fear conditioning in either the hippocampus or amygdala is sufficient to disrupt fear expression after relapse. These results suggest that fear relapse triggers a partial re-emergence of the original fear memory representation, providing new insight into the neural substrates of fear relapse. IntroductionThe biological capacity to produce adaptive behavioral responses in actively changing environments is critical to an animal's survival. Contextual fear conditioning (CFC) is a form of learning whereby an animal learns to associate a conditioned stimulus (i.e. a context) with an unconditioned aversive stimulus (e.g. foot shocks) to produce a conditioned response to the conditioned stimulus (e.g. freezing). Conditioned responses can be mitigated through extinction learning via repeated exposure to the conditioned context in the absence of the foot shock. However, while extinction learning can be effective at attenuating fear, animals are susceptible to fear relapse under several conditions, including exposure to stressors, the passage of time, and re-exposure to the unconditioned stimulus (