Basolateral amygdala activity phase-locked to neocortical slow waves underlies fear memory consolidation

Understanding the neural circuitry involved in fear memory is expected to provide implications for mental disorders such as post-traumatic stress disorder. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) are essential for the consolidation of fear memories. This consolidation occurs in particular when BLA neurons responding to aversive stimuli are reactivated during non-REM sleep. However, the neural circuit mechanism during non-REM sleep remains unclear. We focus on the role of neocortical slow waves, a hallmark of non-REM sleep, in fear memory formation. By recording local field potentials from the mPFC and monitoring BLA neuron activity, we found that BLA neuron firing was concentrated during the late phase of active states (UP states) in slow waves. Using deep whole-cell recordings in vivo, we found that BLA neurons depolarized periodically during the late phases of UP states. We labeled BLA-projecting neurons with channelrhodopsin-2 and found that BLA-projecting neurons in the mPFC also increased firing activity during the late phases of UP states. Finally, when mPFC neurons were optogenetically inhibited during the late phases of UP states in non-REM sleep after fear conditioning, mice exhibited fear behavior even after extinction learning. These results provide insight into the slow-wave synchronization mechanism between the BLA and the mPFC and shed light on the circuit mechanism of fear memory consolidation.