PV-dependent reorganization of prelimbic cortex sub-engrams during systems consolidation

Active ensembles of neurons form an engram during learning. However, engrams are not immutable, and their organization may change with time via systems consolidation. Here, we labeled engram ensembles in the prelimbic (PrL) cortex during contextual fear conditioning. We found that distinct engram subpopulations ("sub-engrams") contribute to memory recall at recent versus remote delays, with sub-engram contribution determined by their projection profile. At recent delays, sub-engrams projecting to the basal amygdala (BA) and lateral entorhinal cortex (LEC) are activated, and their activity is necessary and sufficient for memory retrieval. At remote delays, sub-engrams projecting to the nucleus reuniens (NRe) and nucleus accumbens (NAc) are additionally recruited, and their activity is necessary and sufficient for memory retrieval. Recruitment of NRe- and NAc-projecting sub-engrams to remote recall is an active process, depending on post-training activation of PrL parvalbumin-expressing interneurons. Post-training chemogenetic inhibition of PrL parvalbumin-expressing interneurons prevented sub-engram recruitment and impaired remote memory.