Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events

Abstract

We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the prelimbic cortex (PL) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here we used an hM4Di synaptic-silencing approach to test our hypothesis that specific PL→RE and PL→PER projections regulate sequence memory retrieval. First, we found that suppressing PL activity impaired sequence memory. Second, we found that inhibiting PL→RE and PL→PER pathways effectively abolished sequence memory. Finally, we performed a sequential lag analysis showing that the PL→RE pathway contributes to a working memory retrieval strategy, whereas the PL→PER pathway contributes to a temporal context memory retrieval strategy. These findings demonstrate that the PL→RE and PL→PER pathways serve as top-down mechanisms that control sequence memory retrieval strategies.