Postretrieval Relearning Strengthens Hippocampal Memories via Destabilization and Reconsolidation

Abstract

Memory reconsolidation is hypothesized to be a mechanism by which memories can be updated with new information. Such updating has previously been shown to weaken memory expression or change the nature of the memory. Here we demonstrate that retrieval-induced memory destabilization also allows that memory to be strengthened by additional learning. We show that for rodent contextual fear memories, this retrieval conditioning effect is observed only when conditioning occurs within a specific temporal window opened by retrieval. Moreover, it necessitates hippocampal protein degradation at the proteasome and engages hippocampal Zif268 protein expression, both of which are established mechanisms of memory destabilization-reconsolidation. We also demonstrate a conceptually analogous pattern of results in human visual paired-associate learning. Retrieval-relearning strengthens memory performance, again only when relearning occurs within the temporal window of memory reconsolidation. These findings link retrieval-mediated learning in humans to the reconsolidation literature, and have potential implications both for the understanding of endogenous memory gains and strategies to boost weakly learned memories.SIGNIFICANCE STATEMENT Memory reconsolidation allows existing memories to be updated with new information. Previous research has demonstrated that reconsolidation can be manipulated pharmacologically and behaviorally to impair problematic memories. In this article, we show that reconsolidation can also be exploited to strengthen memory. This is shown both in rats, in a fear memory setting, and in a human declarative memory setting. For both, the behavioral conditions necessary to observe the memory strengthening match those that are required to trigger memory reconsolidation. There are several behavioral approaches that have previously been shown convincingly to strengthen memory. The present demonstration that reconsolidation can underpin long-lasting memory improvements may both provide an underlying mechanism for such approaches and provide new strategies to boost memories.

Keywords: destabilization; fear conditioning; memory; reconsolidation; retrieval.