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

Davis S, Renaudineau S, Poirier R, Poucet B, Save E, Laroche S - Front Behav Neurosci (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre de Neurosciences Paris-Sud, UMR 8195, Univ Paris-Sud Orsay, France.

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.

No MeSH data available.


Related in: MedlinePlus

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 (F1,24 = 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 (F1,24 = 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2992451&req=5

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 (F1,24 = 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 (F1,24 = 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.

Mentions: Experiments so far have demonstrated that object recognition memory can be destabilized after recall, requiring re-stabilization to re-enter a long-term store via a process that involves some but not all of the molecular mechanisms and brain circuits that are engaged in initial consolidation. Here we report novel experiments that extend these findings and demonstrate that object-place recognition memory is also subject to reconsolidation after recall. The first experiment examined the potential role of the ribosomal S6 kinase Rsk2 in consolidation and reconsolidation of object-place recognition memory. The Rsk2 gene encodes a serine/threonine kinase that is activated by and acts downstream of MAPK/ERK via a dual function in CRE-mediated transcriptional regulation and in chromating remodeling by phosphorylating histone H3. In humans, Rsk2 gene mutations are responsible for a very handicapping X-linked form of syndromic mental retardation, the Coffin-Lowry syndrome (reviewed in Hanauer and Young, 2002; Pereira et al., 2010). In a previous experiment, we found that Rsk2 mutant mice have mild impairments in spatial working memory, delayed acquisition, and long-term memory deficits in spatial reference memory, but normal long-term object recognition memory (Poirier et al., 2007b). Thus, we examined whether Rsk2 might have a more prominent role in the more demanding spatial version of recognition memory, object-place recognition. Rsk2 and wild-type (WT) littermates were trained in a circular open-field covered with sawdust and containing three different objects constructed from assembling Lego® pieces. A cardboard cue was placed on the wall of the open-field to serve as a spatial landmark in addition to the multiple visual cues present in the environment. After habituation to the empty open-field for 2 days, Rsk2 and WT mice were given three 5-min trials of exploration of the objects with an inter-trial interval of 5 min. Retention was tested 2 days later during a single 5-min trial by moving one of the objects to a new position. In the reconsolidation experiment, 1 day after training the mice were briefly re-exposed for 5 min to the three objects placed as in the training phase, and retention was tested 1 day later by moving one object to a new location. Analysis of the time spent exploring the displaced object revealed that Rsk2 deficiency did not cause any observable impairment in long-term object-place memory (Figure 1A). In the reconsolidation experiment, WT mice explored the displaced object significantly more than the two non-displaced objects (Figure 1B), demonstrating a similar recognition performance to that when no reactivation was interposed. Surprisingly, however, while post-reactivation short-term memory was intact in Rsk2 deficient mice, post-reactivation long-term memory was completely abolished (Figure 1B). These findings demonstrate that object-place memory is subject to a Rsk2-dependent reconsolidation process following memory reactivation and provide an example of a divergence between mechanisms of consolidation and reconsolidation of recognition memory by showing that the signaling molecule Rsk2 is at least more prominently implicated in object-place memory reconsolidation than in object-place memory consolidation.


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

Davis S, Renaudineau S, Poirier R, Poucet B, Save E, Laroche S - Front Behav Neurosci (2010)

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 (F1,24 = 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 (F1,24 = 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992451&req=5

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 (F1,24 = 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 (F1,24 = 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.
Mentions: Experiments so far have demonstrated that object recognition memory can be destabilized after recall, requiring re-stabilization to re-enter a long-term store via a process that involves some but not all of the molecular mechanisms and brain circuits that are engaged in initial consolidation. Here we report novel experiments that extend these findings and demonstrate that object-place recognition memory is also subject to reconsolidation after recall. The first experiment examined the potential role of the ribosomal S6 kinase Rsk2 in consolidation and reconsolidation of object-place recognition memory. The Rsk2 gene encodes a serine/threonine kinase that is activated by and acts downstream of MAPK/ERK via a dual function in CRE-mediated transcriptional regulation and in chromating remodeling by phosphorylating histone H3. In humans, Rsk2 gene mutations are responsible for a very handicapping X-linked form of syndromic mental retardation, the Coffin-Lowry syndrome (reviewed in Hanauer and Young, 2002; Pereira et al., 2010). In a previous experiment, we found that Rsk2 mutant mice have mild impairments in spatial working memory, delayed acquisition, and long-term memory deficits in spatial reference memory, but normal long-term object recognition memory (Poirier et al., 2007b). Thus, we examined whether Rsk2 might have a more prominent role in the more demanding spatial version of recognition memory, object-place recognition. Rsk2 and wild-type (WT) littermates were trained in a circular open-field covered with sawdust and containing three different objects constructed from assembling Lego® pieces. A cardboard cue was placed on the wall of the open-field to serve as a spatial landmark in addition to the multiple visual cues present in the environment. After habituation to the empty open-field for 2 days, Rsk2 and WT mice were given three 5-min trials of exploration of the objects with an inter-trial interval of 5 min. Retention was tested 2 days later during a single 5-min trial by moving one of the objects to a new position. In the reconsolidation experiment, 1 day after training the mice were briefly re-exposed for 5 min to the three objects placed as in the training phase, and retention was tested 1 day later by moving one object to a new location. Analysis of the time spent exploring the displaced object revealed that Rsk2 deficiency did not cause any observable impairment in long-term object-place memory (Figure 1A). In the reconsolidation experiment, WT mice explored the displaced object significantly more than the two non-displaced objects (Figure 1B), demonstrating a similar recognition performance to that when no reactivation was interposed. Surprisingly, however, while post-reactivation short-term memory was intact in Rsk2 deficient mice, post-reactivation long-term memory was completely abolished (Figure 1B). These findings demonstrate that object-place memory is subject to a Rsk2-dependent reconsolidation process following memory reactivation and provide an example of a divergence between mechanisms of consolidation and reconsolidation of recognition memory by showing that the signaling molecule Rsk2 is at least more prominently implicated in object-place memory reconsolidation than in object-place memory consolidation.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre de Neurosciences Paris-Sud, UMR 8195, Univ Paris-Sud Orsay, France.

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.

No MeSH data available.


Related in: MedlinePlus