Perturbing inhibitory activity interferes with memory reactivation and attenuates learning in postrhinal cortex

Consolidation of salient experiences to form memories rely on precise coupling of high frequency neural network events between hippocampus and neocortex. Within these events, reactivation of subpopulations of neurons is believed to strengthen connections within and between networks. We have previously shown that cue-specific reactivation occurs in postrhinal cortex during learning of a visual association task. Moreover, recent work suggests a role for parvalbumin-expressing (PV) inhibitory interneurons in consolidation by synchronizing hippocampal and cortical activity. We therefore hypothesize that PV interneurons ensure the precise timing between hippocampus and cortex to drive successful reactivations necessary for learning.To investigate this, we trained mice in a visual association task and silenced PV interneurons in visual association cortex after training by chemogenetics on alternating days. We perform two-photon imaging of cell ensembles in postrhinal cortex, during and after daily training. Activity is estimated by RiboL1-jGCaMP8s fluorescence, and PV+ cells identified (and inhibited) by expressing DIO-DREADD-mCherry, or DIO-Ruby3 in control mice. In a separate group we performed simultaneous electrophysiological recordings in visual association cortex and hippocampus area CA1 after daily training.Our results demonstrate that local silencing of PV interneurons post-training strongly attenuates memory consolidation. Notably, the animals’ performance improved following training days with saline injections, and reverted to chance levels following training days with PV silencing. Our results from single-cell and population imaging suggest that reactivations are attenuated after chemogenetic silencing, likely as a result of reduced communication between cortex and hippocampus.