The formation and stability of recognition memory: what happens upon recall?

Abstract

The idea that an already consolidated memory can become destabilized after recall and requires a process of reconsolidation to maintain it for subsequent use has gained much credence over the past decade. Experimental studies in rodents have shown pharmacological, genetic, or injurious manipulation at the time of memory reactivation can disrupt the already consolidated memory. Despite the force of experimental data showing this phenomenon, a number of questions have remained unanswered and no consensus has emerged as to the conditions under which a memory can be disrupted following reactivation. To date most rodent studies of reconsolidation are based on negatively reinforced memories, in particular fear-associated memories, while the storage and stability of forms of memory that do not rely on explicit reinforcement have been less often studied. In this review, we focus on recognition memory, a paradigm widely used in humans to probe declarative memory. We briefly outline recent advances in our understanding of the processes and brain circuits involved in recognition memory and review the evidence that recognition memory can undergo reconsolidation upon reactivation. We also review recent findings suggesting that some molecular mechanisms underlying consolidation of recognition memory are similarly recruited after recall to ensure memory stability, while others are more specifically engaged in consolidation or reconsolidation. Finally, we provide novel data on the role of Rsk2, a mental retardation gene, and of the transcription factor zif268/egr1 in reconsolidation of object-location memory, and offer suggestions as to how assessing the activation of certain molecular mechanisms following recall in recognition memory may help understand the relative importance of different aspects of remodeling or updating long-lasting memories.

Keywords: Coffin Lowry; Rsk2; consolidation; knockout mice; object memory; recognition memory; reconsolidation; zif268/egr1.

Figure 1

Reconsolidation, but not consolidation of spatial, object-place recognition memory is impaired in Rsk2 mutant mice. (A) Rsk2 mutant mice showed no deficit in long-term spatial recognition memory (LTM) over 48 h as they showed preferential exploration of the displaced object (n = 13; t = 3.53; p = 0.0041) as did wild-type (WT) mice (n = 13; t = 9.83; p = 0.0001), with no significant difference in the amount of time spent exploring the displaced object between WT and mutant mice (F_1,24 = 0.416; p = 0.525). (B) In contrast, 24 h after reactivation of the memory, Rsk2 mutant mice showed a deficit as they displayed no preference for the displaced object (t = 1.43; p = 0.17) as opposed to the WT mice (t = 14.61; p = 0.0001); and the level of exploration of the displaced object was significantly greater in WT mice compared with mutant mice (F_1,24 = 70.753; p = 0.0001). Ordinates: percent time spent exploring the displaced object over the mean of the time spent exploring the two non-displaced objects.

Figure 2

Reconsolidation of spatial object-place recognition memory is impaired in zif268 mutant mice. (A) The mice were exposed to a spatial configuration of two objects for eight consecutive sessions (overtraining) on day 1 to alleviate their consolidation deficit and retention was tested 2 days later. In this condition, zif268 mutant mice had normal object-place recognition long-term memory (LTM) as they showed preferential exploration of the displaced object (n = 5; p < 0.05) as WT mice (n = 5; p < 0.05), with no significant difference between WT and mutant mice (F_1,8 = 0.12; p > 0.05). (B) When zif268 mutant mice were briefly re-exposed to the familiar configuration of objects 24 h after training, post-reactivation short-term memory (PR-STM) was intact (left panel). Both WT and zif268 mutant mice preferentially explored the displaced object (p < 0.05 in each case), with no significant difference between groups (F_1,8 = 1.74; p > 0.05). In contrast, post-reactivation long-term memory (PR-LTM) was impaired in zif268 mutant mice (right panel). While WT mice preferentially explored the displaced object (n = 5; p < 0.05), performance of zif268 mutant mice was not different from chance (n = 5; p > 0.05) and there was significant difference between groups (F_1,8 = 6.52; p < 0.05). Ordinates: percent time spent exploring the displaced object over the time spent exploring the non-displaced object.