Coordinated activity and plasticity of infralimbic cortex GABAergic interneurons are critical for fear extinction...

The ability for an organism to encode fear memories is necessary for survival. Once a threat is no longer present, organisms must suppress, or extinguish, this fear memory in favor of other adaptive behaviors. In rodents, the infralimbic cortex (IL) is a locus critical for the extinction of cued fear memory. While this role has been known for decades, the circuit mechanisms underlying its recruitment are largely unknown. By using a combination of immunohistochemistry, neural tagging, in vivo calcium imaging and optogenetics, and optogenetics-assisted brain slice electrophysiology, we revealed that the dynamic activity and plasticity of IL inhibitory interneurons is critical for encoding fear extinction. Specifically, after fear conditioning, IL parvalbumin interneurons exhibit increased activity and plasticity, driving enhanced freezing. After fear extinction, however, IL somatostatin interneurons exhibit extinction cue-associated activity and plasticity, and their activity facilitates extinction memory encoding through inhibition of parvalbumin interneuron activity and disinhibition of IL principal neurons. Further, glutamatergic projections from the basolateral amygdala undergo experience- and cell type-specific plasticity that is required to drive the dynamic recruitment of IL parvalbumin and somatostatin interneurons after fear conditioning and extinction, respectively. Overall, these results reveal the mechanisms of cued fear extinction encoding and highlight critical roles for local IL microcircuit computations in these roles.