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.

Cognition-Enhancing Vagus Nerve Stimulation Alters the Epigenetic Landscape

“…Cycles of learning and memory initiation in the hippocampus followed by cortical consolidation (and reconsolidation) are known to be important for effective cognition (Bekinschtein et al, 2007;Lubin et al, 2008;Tay et al, 2018). A cyclical interpretation of stress-response signaling and epigenetic regulation is also supported by previous reports of oscillations in NF-B and related epigenetic modulators (Nelson et al, 2004;Vanden Berghe et al, 2006;Clayton et al, 2006).…”

Linking Social Cognition to Learning and Memory

“…In addition, the retrieval of engrams is thought to activate CREB, a known enhancer of memory consolidation (Hall et al, 2001) with complementary roles in modulating cellular excitability (Cai et al, 2016;Josselyn and Tonegawa, 2020). We speculate that, when a social engram is reactivated during an observational learning session, similar protein synthesis and LTP processes are active early on, leading to increased CREB and related proteins necessary for memory consolidation and updating (Tay et al, 2019). Consequently, observational fear learning is readily encoded as social information in the brain, likely now causally linked to the social memory of the conspecific.…”

Adult-born neurons immature during learning are necessary for remote memory reconsolidation in rats

“…This additional process which involves de novo protein synthesis is known as memory reconsolidation and highlights that memories are highly plastic and dynamic. The great interest in the reconsolidation process is dual, as on one side it offers a window of opportunity to manipulate memories a long time after the initial encoding, and on the other, it suggests that memory reactivation may play a role in modulating memory strength and in the updating of memory content 2 , 5 , 6 . The understanding of the reconsolidation process is therefore of considerable importance to provide further insights into the development of therapeutic approaches in the treatment of pathological memories 3 , 7 .…”