Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons

Significance This study reveals the roles of PV interneurons surrounding perineuronal nets (PNNs) in both the hippocampus and the anterior cingulate cortex (ACC) in contextual fear memory. We show that increasing PNN expression in these 2 brain structures enhances the recall and reconsolidation of both recent and remote fear memory, corresponding to the enhancement of GABA-related theta oscillations. Conversely, removal of PNNs impairs consolidation and reconsolidation of both recent and remote fear memory via increased feedback inhibition and impairment of theta oscillations. Together, our results suggest that PNNs in the hippocampus and ACC affect behavioral plasticity during the consolidation and reconsolidation of contextual fear memory by regulating feedback inhibition of PV interneurons.