Memory's gatekeeper: the role of PFC in the encoding of familiar events

Abstract

Theoretical models conventionally portray the consolidation of memories as a slow process that unfolds during sleep. According to the classical Complementary Learning Systems (CLS) theory (as presented in J. McClelland et al., 1995), the hippocampus (HPC) rapidly changes its connectivity during wakefulness to encode ongoing events and create memory ensembles that are later transferred to the prefrontal cortex (PFC) during sleep. However, recent experimental studies challenge this notion by showing that new information consistent with prior knowledge can be rapidly consolidated in PFC during wakefulness, and that PFC lesions disrupt the encoding of familiar events in the HPC. These results challenge the widely accepted view that consolidation is a slow process that unfolds during sleep and highlight the role of PFC during the initial stages of memory encoding. The contributions of the PFC to memory encoding have therefore largely been overlooked. Moreover, most theoretical frameworks assume random and uncorrelated patterns representing memories, disregarding the correlations between our experiences. To address this shortcomings, we developed a HPC-PFC network model that simulates interactions between the HPC and PFC during the encoding of a memory (awake stage), and subsequent consolidation (sleeping stage) to examine the contributions of each region to the consolidation of novel and familiar memories. Our results show that the PFC network uses stored memory "schemas" consolidated during previous experiences to identify inputs that evoke familiar patterns of activity, quickly integrated it in its network, and gate which components are encoded in the HPC. More specifically, the PFC uses GABAergic long-range projections to inhibit HPC neurons representing input components correlated with a previously stored memory "schema", eliciting sparse hippocampal activity during exposure to familiar events, as it has been experimentally observed.