Older and stronger object memories are selectively destabilized by reactivation in the presence of new information

Abstract

Reactivation can destabilize previously consolidated memories, rendering them vulnerable to disruption and necessitating a process of reconsolidation in order for them to be maintained. This process of destabilization and reconsolidation has commonly been cited as a means by which established memories can be updated or modified. However, little direct evidence exists to support this view. The present study addressed this issue by analyzing the influence of novel salient information present at the time of memory reactivation on the likelihood of the reactivated memory to become destabilized and vulnerable to disruption. Rats explored sample objects and, some time later, received systemic injections of the N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 or saline prior to memory reactivation. When object memories were relatively young or weakly encoded, MK-801 significantly disrupted reconsolidation regardless of the reactivation conditions. However, increasing the amount of sample object exploration or the interval between the sample phase and reactivation abolished the effect of MK-801 on reconsolidation unless salient novel contextual information was present during memory reactivation. These results highlight the dynamic nature of memory storage and retrieval and indicate an important interaction between the age and strength of a memory, its probability of being destabilized upon reactivation, and the stimulus conditions during reactivation. The essential involvement of novel encoding in destabilizing certain memories supports the idea that the reconsolidation process enables modification of existing memories.

Cholinergic manipulations bidirectionally regulate object memory destabilization

“…There were no significant differences in any of the control measures analyzed (all P . 0.05), indicating that animals in all drug conditions showed similar general object exploration behavior in the sample, reactivation, and choice phases (means and SEMs were consistent with previously established values Winters et al 2009). Control measure values for each experiment are presented in Supplemental Table S1.…”

“…For example, degradation of synaptic proteins via ubiquitin proteasome system (UPS) activation likely underlies the putative synaptic uncoupling of the memory trace that could enable various forms of potential memory modification during the destabilization period (e.g., erasure or weakening, updating, strengthening) (Lee 2008;Lee et al 2008;Choi et al 2010). Despite these advances, few studies have directly addressed the connection between memory destabilization and conditions favoring novel information encoding (Morris et al 2006;Winters et al 2009). Recently, however, Reichelt et al (2013) demonstrated the important role that dopaminergic transmission may play in relation to prediction error.…”

“…These boundary conditions may be related to the putative role of reconsolidation in memory updating (Sara 2000;Rodriguez-Ortiz et al 2005;Morris et al 2006;Hupbach et al 2007;Rossato et al 2007;Lee 2009;Forcato et al 2010;Sevenster et al 2013). Accordingly, stronger or more remote memories may be less likely to be altered in the absence of salient novel information (Lee 2009;Winters et al 2009). Thus, novelty-induced memory destabilization, as the essential gateway to the reconsolidation process, is probably crucial to the adaptive functions of memory modification (Lee 2008(Lee , 2009Choi et al 2010).…”

“…A better understanding of the behavioral and neural factors contributing to memory destabilization is crucial given its permissive role in the reconsolidation process. Indeed, not all memories become labile when reactivated; boundary conditions, including the strength of initial memory encoding and the age of the memory at the time of retrieval, determine the likelihood of destabilization upon reactivation (Milekic and Alberini 2002;Eisenberg and Dudai 2004;Suzuki et al 2004;Winters et al 2009). These boundary conditions may be related to the putative role of reconsolidation in memory updating (Sara 2000;Rodriguez-Ortiz et al 2005;Morris et al 2006;Hupbach et al 2007;Rossato et al 2007;Lee 2009;Forcato et al 2010;Sevenster et al 2013).…”

“…Using the spontaneous object recognition (SOR) paradigm for rats, we previously demonstrated that relatively remote or more strongly encoded object memories were only destabilized when reactivated in the presence of a salient novel contextual cue (a textured floor insert, Winters et al 2009). Our group and others have also previously demonstrated the involvement of the perirhinal cortex (PRh) in object memory reconsolidation (Romero-Granados et al 2010;Winters et al 2011;Balderas et al 2013).…”