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.

Figure 1.

a, b, Schematic representation of the infusion needle tip placements from typical groups of animals with PRh implantations (a) (Experiment 3, reactivation group; n = 10) and HPC implantations (b) (Experiment 4, reactivation group; n = 8). These placements are representative of needle tip locations in all animals included in the behavioral analyses of the present study. Cannulas in PRh were consistently located between 5.80 and 6.30 mm posterior to bregma. Cannulas in HPC for all animals were located at ∼3.6 mm posterior to bregma. Some needle tips overlap in the figure. Brain section illustrations modified from Paxinos and Watson (1998). c and d are photomicrographs illustrating PRh and dorsal HPC cannula tracks, respectively; arrows indicate tips of infusion cannula tracks. Dashed lines surrounding placements in a approximate the borders of PRh as defined by Burwell (2001).

Figure 2.

Spontaneous object recognition performance of rats in Experiment 1. Intra-PRh administration of anisomycin immediately following the standard reactivation phase prevented object memory reconsolidation. Perirhinal protein synthesis inhibition did not affect object recognition memory in rats that did not undergo a memory reactivation phase before drug delivery. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions. *p < 0.05 (anisomycin vs saline in reactivation group).

Figure 3.

Spontaneous object recognition performance of rats in Experiment 2. Intra-HPC administration of anisomycin immediately following the standard reactivation phase did not affect object memory reconsolidation. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions.

Figure 4.

Spontaneous object recognition performance of rats in Experiment 3. Intra-PRh administration of anisomycin immediately following memory reactivation in the presence of a novel object prevented reconsolidation of the sample object trace. Inhibition of protein synthesis in PRh did not affect object recognition memory in rats that did not undergo a memory reactivation phase before drug delivery. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions. ***p < 0.001 (anisomycin vs saline in reactivation group).

Figure 5.

Spontaneous object recognition performance of rats in Experiment 4. Intra-HPC administration of anisomycin immediately following memory reactivation in the presence of a novel object did not affect reconsolidation of the sample object trace. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions.

Figure 6.

Spontaneous object recognition performance of rats in Experiment 5. Intra-PRh administration of anisomycin immediately following memory reactivation in the presence of a novel contextual cue blocked reconsolidation of the sample object trace. Perirhinal protein synthesis inhibition did not affect object recognition memory in rats that did not undergo a memory reactivation phase before drug delivery. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions. *p < 0.05 (anisomycin vs saline in reactivation group).

Figure 7.

Spontaneous object recognition performance of rats in Experiment 6. Intra-HPC administration of anisomycin immediately following memory reactivation in the presence of a novel contextual cue prevented reconsolidation of the sample object trace. Inhibition of hippocampal protein synthesis did not affect object recognition memory in rats that did not undergo a memory reactivation phase before drug delivery. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions. *p < 0.05 (anisomycin vs saline in reactivation group).

Figure 8.

Spontaneous object recognition performance of rats in Experiment 7. Crossed unilateral administration of anisomycin into PRh and HPC immediately following memory reactivation in the presence of a novel contextual cue prevented reconsolidation of the sample object trace. Inhibition of protein synthesis did not affect object recognition memory in rats that did not undergo a memory reactivation phase before drug delivery. Data are presented as average discrimination ratio (±SEM) from the choice phase administered 24 h after drug infusions. **p < 0.01 (anisomycin vs saline in reactivation group).