The Yin and Yang of Memory Consolidation: Hippocampal and Neocortical

While hippocampal and cortical mechanisms of memory consolidation have long been studied, their interaction is poorly understood. We sought to investigate potential interactions with respect to trace dominance, strengthening, and interference associated with postencoding novelty or sleep. A learning procedure was scheduled in a watermaze that placed the impact of novelty and sleep in opposition. Distinct behavioural manipulations—context preexposure or interference during memory retrieval—differentially affected trace dominance and trace survival, respectively. Analysis of immediate early gene expression revealed parallel up-regulation in the hippocampus and cortex, sustained in the hippocampus in association with novelty but in the cortex in association with sleep. These findings shed light on dynamically interacting mechanisms mediating the stabilization of hippocampal and neocortical memory traces. Hippocampal memory traces followed by novelty were more dominant by default but liable to interference, whereas sleep engaged a lasting stabilization of cortical traces and consequent trace dominance after preexposure.Author Summary: Memories are initially stored in a hippocampal–cortical network; however, which brain area is important for long-term storage depends on what happens after learning. For example, replay of recent memories during sleep is thought to lead to consolidation in the cortex. In contrast, postlearning novelty is thought to strengthen hippocampal memory traces via a mechanism that depends on dopamine.