Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction

Learned fear and safety are associated with distinct oscillatory states in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). To determine if and how these network states support the retrieval of competing memories, we mimicked endogenous oscillatory activity through optogenetic stimulation of parvalbumin-expressing interneurons in mice during retrieval of contextual fear and extinction memories. We found that exogenously induced 4Hz and 8Hz oscillatory activity in the BLA exerts bi-directional control over conditioned freezing behavior in an experience- and context-specific manner, and that these oscillations have an experience-dependent ability to recruit distinct functional neuronal ensembles. At the network level we demonstrate, via simultaneous manipulation of BLA and mPFC, that experience-dependent 4Hz resonance across BLA-mPFC circuitry supports post-extinction fear memory retrieval. Our findings reveal that post-extinction fear memory retrieval is supported by local and interregional experience-dependent resonance, and suggest novel approaches for interrogation and therapeutic manipulation of acquired fear circuitry. Theta range oscillations in the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) are associated with conditioned fear. Here, the authors use exogenous oscillatory stimulation of the BLA and mPFC in mice to determine the dynamic roles of theta-range oscillatory states across conditioned fear and extinction learning.