On the Dynamic Nature of the Engram: Evidence for Circuit-Level Reorganization of Object Memory Traces following Reactivation

Abstract

Research has implicated the perirhinal cortex (PRh) in several aspects of object recognition memory. The specific role of the hippocampus (HPC) remains controversial, but its involvement in object recognition may pertain to processing contextual information in relation to objects rather than object representation per se. Here we investigated the roles of the PRh and HPC in object memory reconsolidation using the spontaneous object recognition task for rats. Intra-PRh infusions of the protein synthesis inhibitor anisomycin immediately following memory reactivation prevented object memory reconsolidation. Similar deficits were observed when a novel object or a salient contextual change was introduced during the reactivation phase. Intra-HPC infusions of anisomycin, however, blocked object memory reconsolidation only when a contextual change was introduced during reactivation. Moreover, disrupting functional interaction between the HPC and PRh by infusing anisomycin unilaterally into each structure in opposite hemispheres also impaired reconsolidation when reactivation was done in an altered context. These results show for the first time that the PRh is critical for reconsolidation of object memory traces and provide insight into the dynamic process of object memory storage; the selective requirement for hippocampal involvement following reactivation in an altered context suggests a substantial circuit level object trace reorganization whereby an initially PRh-dependent object memory becomes reliant on both the HPC and PRh and their interaction. Such trace reorganization may play a central role in reconsolidation-mediated memory updating and could represent an important aspect of lingering consolidation processes proposed to underlie long-term memory modulation and stabilization.

Cholinergic manipulations bidirectionally regulate object memory destabilization

“…The intra-PRh result is consistent with numerous studies implicating PRh in object memory processing, including reconsolidation (Buckley 2005;Murray et al 2007;Winters et al 2008Winters et al , 2011Brown et al 2012;Balderas et al 2013). Furthermore, stimulating muscarinic receptors during memory reactivation with systemic or intra-PRh delivery of muscarinic receptor agonists mimicked the memory destabilizing effects of salient novelty; when strongly encoded or relatively remote memories were reactivated in the absence of the contextual change, they were not destabilized unless oxotremorine or carbachol was administered prior to the reactivation phase.…”

“…Rats also showed significant novel object preference in all conditions (all P , 0.01), except for saline/anisomycin (P ¼ 0.738). We have previously demonstrated that the intra-PRh blockade of object memory destabilization is reactivation-dependent (Winters et al 2011).…”

“…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). Given the established role of ACh in information encoding in the SOR task (Warburton et al 2003;Winters et al 2006Winters et al , 2007, we hypothesized that the novelty-induced object memory destabilization demonstrated in our previous study was triggered by cholinergic transmission at muscarinic receptors within PRh.…”

Retrieval is not necessary to trigger reconsolidation of object recognition memory in the perirhinal cortex

“…P-values ,0.05 were accepted as statistical significance. The first minute of exploration was used for statistical analysis (reactivation and test phases), since it was reported that novel objects discrimination is more evident during that period of time (Dix and Aggleton 1999;Mumby et al 2002;Winters et al 2011).To test whether pharmacological inhibition of AMPA receptors disrupts retrieval of ORM we infused vehicle or CNQX 15 min before memory reactivation in the perirhinal cortex. Rats were exposed to two copies of the same object in the sample phase (Fig.…”

“…Importantly, STM was unaffected by AP5. Experiments in which protein synthesis was inhibited by anisomycin infusion into the perirhinal cortex showed that this region is indispensable for the occurrence of ORM reconsolidation (Winters et al 2011). In another study, it was established that glutamate receptors in the perirhinal cortex play a role in ORM formation.…”