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Memory consolidation. (A) Immediately after the last training session, mice received injections of ANI or NaCl. The probe test took place 24 h after the injections. (B) Number of annulus crossings during the 60-s probe trial. Anisomycin injection in the hippocampal CA3 region just after training impaired spatial memory consolidation. ***P < 0.001.
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Our understanding of the memory reconsolidation process is at an earlier stage than that of consolidation. For example, it is unclear if, as for memory consolidation, reconsolidation of a memory trace necessitates protein synthesis. In fact, conflicting results appear in the literature and this discrepancy may be due to differences in the experimen...
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Context 1
... shown in Figure 3, ANI injection just after initial acquisi- tion impaired long-term retention during the probe test per- formed 24 h later. A two-way ANOVA revealed no significant effect between VEH-and ANI-injected mice [F (1,64) 5 0.105; P 5 0.747] on the total number of annulus crossings, but a significant quadrant effect [F (3,64) 5 20.504; P < 0.001] and a significant treatment x quadrant interaction [F (3,64) 5 8.921; P < 0.001] indicating that the profile of ex- ploration of the quadrants was different in the two groups of mice. ...
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Citations
... 49 Reconsolidation of spatial reference memory requires activation of transcriptional machinery and new protein synthesis in the dHPC, 50,51 especially in the dCA3. 52 It may be possible that dCA3 CtBP2 deficiency interfered gene expression that is indispensable for spatial memory reconsolidation, and thus impaired spatial memory in KD mice. Intriguingly, CP-AMPARs have been implicated in memory reconsolidation. ...
The dorsal hippocampus plays a pivotal role in spatial memory. However, the role of subregion‐specific molecular pathways in spatial cognition remains unclear. We observed that the transcriptional coregulator C‐terminal binding protein 2 (CtBP2) presented CA3‐specific enrichment in expression. RNAi interference of CtBP2 in the dorsal CA3 (dCA3) neurons, but not the ventral CA3 (vCA3), specifically impaired spatial reference memory and reduced the expression of GluR2, the calcium permeability determinant subunit of AMPA receptors. Application of an antagonist for GluR2‐absent calcium permeable AMPA receptors rescued spatial memory deficits in dCA3 CtBP2 knockdown animals. Transcriptomic analysis suggest that CtBP2 may regulate GluR2 protein level through post‐translational mechanisms, especially by the endocytosis pathway which regulates AMPA receptor sorting. Consistently, CtBP2 deficiency altered the mRNA expression of multiple endocytosis‐regulatory genes, and CtBP2 knockdown in primary hippocampal neurons enhanced GluR2‐containing AMPA receptor endocytosis. Together, our results provide evidence that the dCA3 regulates spatial reference memory by the CtBP2/GluR2 pathway through the modulation of calcium permeable AMPA receptors.
... Une majorité d'études utilisent un probe-test de rétention en tant que rappel (Morris et al., 2006;Rossato, 2006;Bonini et al., 2007;Da Silva et al., 2008;Kim et al., 2011). D'autres ont également réussit à réactiver la mémoire en utilisant un nouvel essai d'apprentissage (Artinian et al., 2007(Artinian et al., , 2008De Jaeger et al., 2014), ce qui n'est pas le cas de Rossato, (2006 (Morris et al., 2006) Anisomycine HP dorsal 0h souris 6j (DMP) 2j 60s probe 1j (Morris et al., 2006) Anisomycine HP dorsal 0h (pas 3 ni 6h) rat 5j 1j 60s probe 2h -1j -5j (Rossato, 2006) Anisomycine HP dorsal 0h rat 5j 5j 60s probe 2h -1j -5j (Rossato, 2006) Anisomycine HP dorsal 0h rat 5j 5j essai 2h -1j -5j (Rossato, 2006) Inhibition de la PKC 0h rat 5j 1j 60s probe 1j (Bonini et al., 2007) Inhibition de la PKC 0h rat 1j (16 essais) 1j 60s probe 1j (Bonini et al., 2007) Inhibition de la PKC 0h rat 1j (16 essais) 5j 60s probe 5j (Bonini et al., 2007) Anisomycine HP dorsal 0h souris 2j 1j 60s probe 1j Inhibition de CREB -6h souris 2j 1j 60s probe 1j Anisomycine HP dorsal -20min rat 3j 7j 60s probe + essai 7j (Rodriguez-Ortiz et al., 2008) Anisomycine HP dorsal -20min rat 5j 7j 60s probe + essai 7j (Rodriguez-Ortiz et al., 2008) Anisomycine CA3 ou inhibition de la dégradation protéique 0h (pas 2, 4 ni 6h) souris 1j (12 essais) 1j essai 1j (Artinian et al., 2007(Artinian et al., , 2008De Jaeger et al., 2014) Anisomycine CA3 ou inhibition de la dégradation protéique 0h souris 1j (12 essais) 1j essai 1h (Artinian et al., 2007(Artinian et al., , 2008 Anisomycine CA3 0h souris 1j (12 essais) 1j 120s sur la PF immergée ou non 1j (Artinian et al., 2007) Anisomycine CA3 0h souris 1j (12 essais) 1j 10min dans la salle + lumière rouge 1j (Artinian et al., 2007) Anisomycine CA3 mais pas CCa 0h souris 1j (12 essais) 1j essai 1j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 12j (1 essai/j) 1j essai 1j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 1j (24 essais) 1j essai 1j -7j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 1j (24 essais) 1j essai + NI 1j (De Jaeger et al., 2014) Méthamphétamine 0h souris 5j 1j 60s probe 1j (Cao et al., 2013) Anisomycine i-p -30min souris 2j 1j 60s probe 1j (Suzuki, 2004) Anisomycine i-p -30min souris 2j 1j 60s probe x 10 1j (Suzuki, 2004) Figure 9 : Etudes caractérisant la reconsolidation de la mémoire spatiale dans le WM. HP : hippocampe. ...
... Une majorité d'études utilisent un probe-test de rétention en tant que rappel (Morris et al., 2006;Rossato, 2006;Bonini et al., 2007;Da Silva et al., 2008;Kim et al., 2011). D'autres ont également réussit à réactiver la mémoire en utilisant un nouvel essai d'apprentissage (Artinian et al., 2007(Artinian et al., , 2008De Jaeger et al., 2014), ce qui n'est pas le cas de Rossato, (2006 (Morris et al., 2006) Anisomycine HP dorsal 0h souris 6j (DMP) 2j 60s probe 1j (Morris et al., 2006) Anisomycine HP dorsal 0h (pas 3 ni 6h) rat 5j 1j 60s probe 2h -1j -5j (Rossato, 2006) Anisomycine HP dorsal 0h rat 5j 5j 60s probe 2h -1j -5j (Rossato, 2006) Anisomycine HP dorsal 0h rat 5j 5j essai 2h -1j -5j (Rossato, 2006) Inhibition de la PKC 0h rat 5j 1j 60s probe 1j (Bonini et al., 2007) Inhibition de la PKC 0h rat 1j (16 essais) 1j 60s probe 1j (Bonini et al., 2007) Inhibition de la PKC 0h rat 1j (16 essais) 5j 60s probe 5j (Bonini et al., 2007) Anisomycine HP dorsal 0h souris 2j 1j 60s probe 1j Inhibition de CREB -6h souris 2j 1j 60s probe 1j Anisomycine HP dorsal -20min rat 3j 7j 60s probe + essai 7j (Rodriguez-Ortiz et al., 2008) Anisomycine HP dorsal -20min rat 5j 7j 60s probe + essai 7j (Rodriguez-Ortiz et al., 2008) Anisomycine CA3 ou inhibition de la dégradation protéique 0h (pas 2, 4 ni 6h) souris 1j (12 essais) 1j essai 1j (Artinian et al., 2007(Artinian et al., , 2008De Jaeger et al., 2014) Anisomycine CA3 ou inhibition de la dégradation protéique 0h souris 1j (12 essais) 1j essai 1h (Artinian et al., 2007(Artinian et al., , 2008 Anisomycine CA3 0h souris 1j (12 essais) 1j 120s sur la PF immergée ou non 1j (Artinian et al., 2007) Anisomycine CA3 0h souris 1j (12 essais) 1j 10min dans la salle + lumière rouge 1j (Artinian et al., 2007) Anisomycine CA3 mais pas CCa 0h souris 1j (12 essais) 1j essai 1j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 12j (1 essai/j) 1j essai 1j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 1j (24 essais) 1j essai 1j -7j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 1j (24 essais) 1j essai + NI 1j (De Jaeger et al., 2014) Méthamphétamine 0h souris 5j 1j 60s probe 1j (Cao et al., 2013) Anisomycine i-p -30min souris 2j 1j 60s probe 1j (Suzuki, 2004) Anisomycine i-p -30min souris 2j 1j 60s probe x 10 1j (Suzuki, 2004) Figure 9 : Etudes caractérisant la reconsolidation de la mémoire spatiale dans le WM. HP : hippocampe. ...
... Une majorité d'études utilisent un probe-test de rétention en tant que rappel (Morris et al., 2006;Rossato, 2006;Bonini et al., 2007;Da Silva et al., 2008;Kim et al., 2011). D'autres ont également réussit à réactiver la mémoire en utilisant un nouvel essai d'apprentissage (Artinian et al., 2007(Artinian et al., , 2008De Jaeger et al., 2014), ce qui n'est pas le cas de Rossato, (2006 (Morris et al., 2006) Anisomycine HP dorsal 0h souris 6j (DMP) 2j 60s probe 1j (Morris et al., 2006) Anisomycine HP dorsal 0h (pas 3 ni 6h) rat 5j 1j 60s probe 2h -1j -5j (Rossato, 2006) Anisomycine HP dorsal 0h rat 5j 5j 60s probe 2h -1j -5j (Rossato, 2006) Anisomycine HP dorsal 0h rat 5j 5j essai 2h -1j -5j (Rossato, 2006) Inhibition de la PKC 0h rat 5j 1j 60s probe 1j (Bonini et al., 2007) Inhibition de la PKC 0h rat 1j (16 essais) 1j 60s probe 1j (Bonini et al., 2007) Inhibition de la PKC 0h rat 1j (16 essais) 5j 60s probe 5j (Bonini et al., 2007) Anisomycine HP dorsal 0h souris 2j 1j 60s probe 1j Inhibition de CREB -6h souris 2j 1j 60s probe 1j Anisomycine HP dorsal -20min rat 3j 7j 60s probe + essai 7j (Rodriguez-Ortiz et al., 2008) Anisomycine HP dorsal -20min rat 5j 7j 60s probe + essai 7j (Rodriguez-Ortiz et al., 2008) Anisomycine CA3 ou inhibition de la dégradation protéique 0h (pas 2, 4 ni 6h) souris 1j (12 essais) 1j essai 1j (Artinian et al., 2007(Artinian et al., , 2008De Jaeger et al., 2014) Anisomycine CA3 ou inhibition de la dégradation protéique 0h souris 1j (12 essais) 1j essai 1h (Artinian et al., 2007(Artinian et al., , 2008 Anisomycine CA3 0h souris 1j (12 essais) 1j 120s sur la PF immergée ou non 1j (Artinian et al., 2007) Anisomycine CA3 0h souris 1j (12 essais) 1j 10min dans la salle + lumière rouge 1j (Artinian et al., 2007) Anisomycine CA3 mais pas CCa 0h souris 1j (12 essais) 1j essai 1j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 12j (1 essai/j) 1j essai 1j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 1j (24 essais) 1j essai 1j -7j (De Jaeger et al., 2014) Anisomycine CA3 0h souris 1j (24 essais) 1j essai + NI 1j (De Jaeger et al., 2014) Méthamphétamine 0h souris 5j 1j 60s probe 1j (Cao et al., 2013) Anisomycine i-p -30min souris 2j 1j 60s probe 1j (Suzuki, 2004) Anisomycine i-p -30min souris 2j 1j 60s probe x 10 1j (Suzuki, 2004) Figure 9 : Etudes caractérisant la reconsolidation de la mémoire spatiale dans le WM. HP : hippocampe. ...
La neurogenèse hippocampique adulte fait référence à la création de neurones durant la vie adulte dans le gyrus denté de l’hippocampe. Une décennie de recherche a démontré l’importance de cette neurogenèse chez l’adulte dans les processus de mémoire. En particulier, la neurogenèse adulte est nécessaire à l’apprentissage spatial et l’apprentissage spatial lui-même augmente la survie et accélère le développement d’une population de nouveaux neurones immatures. Cependant, l’implication de ces nouveaux neurones « sélectionnés » par l’apprentissage dans le devenir de la mémoire reste incertaine. En conséquence, le travail de cette thèse porte sur l’étude du rôle de ces nouveaux neurones dans les processus de mémoire spatiale à long terme résultants de l’apprentissage d’origine, comme la restitution et la reconsolidation de la mémoire. En effet depuis plus d’un siècle, on sait qu’un apprentissage n’induit pas immédiatement une mémoire stable. Les souvenirs sont tout d’abord fragiles, puis vont au fil du temps devenir stables et insensibles aux perturbations via un processus appelé «consolidation de la mémoire». Cependant ce processus n’est pas immuable ; les souvenirs établis peuvent à nouveau devenir labiles lorsqu'ils sont rappelés ou réactivés lors d’une restitution de la mémoire. Cette déstabilisation d’une mémoire consolidée nécessite alors un nouveau processus de stabilisation appelé « reconsolidation de la mémoire ». Depuis sa découverte, la reconsolidation a vivement intéressé le milieu de la recherche sur la mémoire et un nombre croissant d’études a cherché à comprendre les mécanismes sous-tendant cette reconsolidation, en particulier dans l'hippocampe. Étonnamment, le processus de reconsolidation n’a été que très peu envisagé dans le contexte de la neurogenèse hippocampique adulte.Nous avons tout d’abord mis au point un protocole de reconsolidation de la mémoire spatiale du rat dans le labyrinthe aquatique de Morris. Cela nous a permis de montrer que les néo-neurones nés avant l’apprentissage étaient activés lors de la reconsolidation de la mémoire spatiale, ce qui n’est pas le cas des neurones issus du développement précoce. Afin de pouvoir établir une relation de causalité entre néo-neurones et processus de reconsolidation, nous avons ensuite développé un outil basé sur la technique pharmacogénétique des DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) couplés à un rétrovirus. Cet outil permet de marquer les néo-neurones à leur naissance et de les manipuler (inhiber ou stimuler l’activation) plus tard, lors des processus de mémoire à long terme. Nous avons observé que les néo-neurones immatures modifiés par l’apprentissage étaient non seulement activés par la reconsolidation mais également nécessaire à celle-ci, à l’inverse des néo-neurones matures au moment de l’apprentissage. Nous avons enfin montré que stimuler l’activité des néo-neurones au moment de la restitution de la mémoire améliorait les performances des rats dans le labyrinthe aquatique.Ensemble, ces résultats de thèse soulignent le rôle critique de la neurogenèse hippocampique adulte dans la stabilisation de la mémoire spatiale à long terme.
... Recent advances in neuroscience research have shown that, each time a memory is reactivated, the memory trace returns to an active labile state and must undergo reconsolidation in order to be maintained in the inactive stable state [10][11][12][13]. The majority of memory reconsolidation studies used protein synthesis inhibitors, and showed that, similarly to initial consolidation, memory reconsolidation requires new protein synthesis [12,13], notably for hippocampus-dependent memories [14][15][16][17]. ...
Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the “city-like” test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.
... The transcriptional activation of the short Homer1 isoforms after contextual fear memory retrieval may be related to the hippocampal-dependent memory processes of reconsolidation and extinction associated with short and prolonged conditioned context exposure, respectively [63,89,90]. These findings encourage the study of the contribution of Homer1a and Ania-3 to post retrieval plasticity mechanisms, particularly with regard to their roles in distinct hippocampal subregions that may themselves differentially contribute to extinction and reconsolidation [84,85,[91][92][93]. This is the first time that evidence for a role of short Homer isoforms in retrieval-related memory processes, including extinction learning, has been presented. ...
Genes involved in synaptic plasticity, particularly genes encoding postsynaptic density proteins, have been recurrently linked to psychiatric disorders including schizophrenia and autism. Postsynaptic density Homer1 proteins contribute to synaptic plasticity through the competing actions of short and long isoforms. The activity-induced expression of short Homer1 isoforms, Homer1a and Ania-3 , is thought to be related to processes of learning and memory. However, the precise regulation of Homer1a and Ania-3 with different components of learning has not been investigated. Here, we used in situ hybridization to quantify short and long Homer1 expression in the hippocampus following consolidation, retrieval, and extinction of associative fear memory, using contextual fear conditioning in rats. Homer1a and Ania-3 , but not long Homer1 , were regulated by contextual fear learning or novelty detection, although their precise patterns of expression in hippocampal subregions were dependent on the isoform. We also show for the first time that the two short Homer1 isoforms are regulated after the retrieval and extinction of contextual fear memory, albeit with distinct temporal and spatial profiles. These findings support a role of activity-induced Homer1 isoforms in learning and memory processes in discrete hippocampal subregions and suggest that Homer1a and Ania-3 may play separable roles in synaptic plasticity.
... e l s e v i e r . c o m / l o c a t e / y n l m e and mRNA in the amygdala and hippocampus, close in time to memory reactivation, produces a retention deficit, thus supporting the reconsolidation hypothesis (e.g., Artinian, De Jaeger, Fellini, de Saint Blanquat, & Roullet, 2007;Da Silva et al., 2008;Debiec, LeDeux, & Nader, 2002;Duvarci, Nader, & LeDoux, 2008;Parsons, Gafford, Baruch, Riedner, & Helmstetter, 2006;Pedroso et al., 2013). In sharp contrast, other authors reported no deficiencies in retention after interference with transcription (Izquierdo, Cammarota, Vianna, & Bevilaqua, 2004;Parsons et al., 2006;Pedroso et al., 2013) and translation in those structures, as well as in other structures, e.g. ...
It has been found that interference with neural activity after a consolidated memory is retrieved produces an amnestic state; this has been taken has indicative of destabilization of the memory trace that would have been produced by a process of reconsolidation (allowing for maintenance of the original trace). However, a growing body of evidence shows that this is not a reliable effect, and that it is dependent upon some experimental conditions, such as the age of the memory, memory reactivation procedures, the predictability of the reactivation stimulus, and strength of training. In some instances, where post-retrieval treatments induce a retention deficit (which would be suggestive of interference with reconsolidation), memory is rescued by simple passing of time or by repeated retention tests. We now report that post-training and post-retrieval inhibition of transcription and translation in dorsal striatum, a structure where both of these manipulations have not been studied, produce interference with consolidation and a transitory retention deficit, respectively. These results do not give support to the reconsolidation hypothesis and lead to the conclusion that the post-activation deficiencies are due to interference with retrieval of information.
... Concerning the classic MWM, the reactivation trial consisted in an additional training trial, suggesting no prediction error was generated during memory reactivation, so preventing maybe the induction of reconsolidation. However, in our lab, using exactly the same behavioral procedure used as the present study (Artinian et al., 2007(Artinian et al., , 2008, we obtained a clear amnesic effect with an injection of protein synthesis inhibitor during reactivation. Thus, in our experimental condition, the reactivation trial induced memory reconsolidation and despite the longer duration of training and the multiple training trials (i.e., a potential difference in memory strength), post reactivation anisomycin impaired subsequent spatial memory performances. ...
Memory reconsolidation impairment using the β-noradrenergic receptor blocker propranolol is a promising novel treatment avenue for patients suffering from pathogenic memories, such as post-traumatic stress disorder (PTSD). However, in order to better inform targeted treatment development, the effects of this compound on memory need to be better characterized via translational research. We examined the effects of systemic propranolol administration in mice undergoing a wide range of behavioral tests to determine more specifically which aspects of the memory consolidation and reconsolidation are impaired by propranolol. We found that propranolol (10 mg/kg) affected memory consolidation in non-aversive tasks (object recognition and object location) but not in moderately (Morris water maze (MWM) to highly (passive avoidance, conditioned taste aversion) aversive tasks. Further, propranolol impaired memory reconsolidation in the most and in the least aversive tasks, but not in the moderately aversive task, suggesting its amnesic effect was not related to task aversion. Moreover, in aquatic object recognition and location tasks in which animals were forced to behave (contrary to the classic versions of the tasks); propranolol did not impair memory reconsolidation. Taken together our results suggest that the memory impairment observed after propranolol administration may result from a modification of the emotional valence of the memory rather than a disruption of the contextual component of the memory trace. This is relevant to the use of propranolol to block memory reconsolidation in individuals with PTSD, as such a treatment would not erase the traumatic memory but only reduce the emotional valence associated with this event.
... Two probe trials were sequentially carried out after mice learned to find the hidden platform (Fig. 2 E and F). To avoid possible memory extinction, a short probe trial of 60 s was used as memory reactivation session, which has been shown by other groups to cause no extinction (17)(18)(19). The first probe test was carried out 1 d after spatial training, and both Arrb2 −/− mice and wild-type littermates demonstrated a similar preference for the target quadrant. ...
Significance
β-Adrenergic receptors (β-ARs) are hormone and neurotransmitter receptors. The data we present in this paper challenge the assumption that memory reconsolidation is governed by the traditional β-AR/G protein signaling pathway. We found that memory reconsolidation is mediated by a β-arrestin–dependent β-adrenergic signaling pathway. Our experiments demonstrate that upon memory retrieval, a β1-AR/β-arrestin2/ERK pathway is activated in distinct brain areas, stimulating de novo protein synthesis and inducing postretrieval memory restabilization. Moreover, memory reconsolidation can be disrupted by propranolol, but not biased β-blockers such as carvedilol and alprenolol. Our study thus demonstrates that memory reconsolidation is mediated by a β-arrestin–biased β-adrenergic signaling pathway and reveals the therapeutic potential for β-arrestin–biased ligands in the treatment of memory-related disorders.
... The experimental context has been shown to be a sufficient reminder to trigger reconsolidation in humans (Hupbach et al., 2008) and rodents (Artinian, De Jaeger, Fellini, de Saint Blanquat, & Roullet, 2007). In Experiment 1.1, we manipulated the context (visual, odor, and texture cues) in which the second set of feeders (Set 2) was learned in order to either remind or not remind rats of a previously learned set (Set 1). ...
... This result replicates previous findings using the same tasks (Hupbach et al., 2008;Jones et al., 2012). Re-exposure to the experimental context has been shown to be sufficient to induce reactivation and reconsolidation (Artinian et al., 2007;Sara, 2010). Therefore, in young animals, re-entering the Set 1 learning context on Day 2 may have triggered reactivation of the Set 1 memory, allowing the newly learned Set 2 items to be integrated into the Set 1 memory. ...
There is strong evidence that hippocampal memory returns to a labile state upon reactivation, initiating a reconsolidation process that restabilizes it and allows for its updating. Normal aging is associated with deficits in episodic memory processes. However, the effects of aging on memory reconsolidation and its neural substrate remain largely unknown, and an animal model is lacking. In this study we investigated the effects of aging on context-dependent reconsolidation using an episodic set-learning task in humans and an analogous set-learning spatial task in rats. In both tasks, young and older subjects learned a set of objects (humans) or feeders (rats; Set 1) in Context A on Day 1. On Day 2, a different set (Set 2) was learned in either Context A (Reminder condition) or Context B (No Reminder condition). On Day 3, subjects were instructed (humans) or cued (rats) to recall Set 1. Young rats and humans in the Reminder condition falsely recalled significantly more items from Set 2 than those in the No Reminder condition, suggesting that the reminder context triggered a reactivation of Set 1 on Day 2 and allowed the integration of Set 2 items into Set 1. In both species, older subjects displayed a different pattern of results than young subjects. In aged rats, there was no difference between conditions in the level of falsely recalled Set 2 items (intrusions). Older humans in the No Reminder condition made significantly more intrusions than those in the Reminder condition. Follow-up control experiments in aged rats suggested that intrusions in older animals reflected general interference independent of context manipulations. We conclude that contextual reminders are not sufficient to trigger memory updating in aged rats or aged humans, unlike in younger individuals. Further studies using this animal model should further our understanding of the role of the hippocampus in memory maintenance and updating during normal aging.
... Indeed, the reactivation of a previously consolidated memory trace can render it labile again. If this memory reactivated trace is destabilized, in order to end this labile state, this trace must undergo a restabilization process called "reconsolidation" which requires new protein synthesis (Sara 2000;Nader 2003), notably for hippocampal-dependent memories (Debiec et al. 2002;Rossato et al. 2006;Artinian et al. 2007Artinian et al. , 2008. Furthermore, the need for protein synthesis following memory reactivation has been found in different kinds of learning and memory using various tests such as fear conditioning (Nader et al. 2000), object recognition (Akirav and Maroun 2006), appetitive instrumental learning (Hernandez et al. 2002), eyelid conditioning responses (Inda et al. 2005), and spatial learning in the Morris water maze (MWM) (Rossato et al. 2006;Artinian et al. 2007Artinian et al. , 2008. ...
... If this memory reactivated trace is destabilized, in order to end this labile state, this trace must undergo a restabilization process called "reconsolidation" which requires new protein synthesis (Sara 2000;Nader 2003), notably for hippocampal-dependent memories (Debiec et al. 2002;Rossato et al. 2006;Artinian et al. 2007Artinian et al. , 2008. Furthermore, the need for protein synthesis following memory reactivation has been found in different kinds of learning and memory using various tests such as fear conditioning (Nader et al. 2000), object recognition (Akirav and Maroun 2006), appetitive instrumental learning (Hernandez et al. 2002), eyelid conditioning responses (Inda et al. 2005), and spatial learning in the Morris water maze (MWM) (Rossato et al. 2006;Artinian et al. 2007Artinian et al. , 2008. ...
... In the present study, we assessed the necessity of protein synthesis in the hippocampal CA3 area during the reconsolidation process (Artinian et al. 2007(Artinian et al. , 2008 according to the spatial memory trace's age, level of acquisition, and need for an update. Finally, we investigated whether the anterior cingulate cortex (aCC), a neocortical region known to process remote memories , could replace the hippocampal CA3 in these conditions and would be the site of protein synthesis-dependent reconsolidation. ...
Reconsolidation is necessary for the restabilization of reactivated memory traces. However, experimental parameters have been suggested as boundary conditions for this process. Here we investigated the role of a spatial memory trace's age, strength, and update on the reconsolidation process in mice. We first found that protein synthesis is necessary for reconsolidation to occur in the hippocampal CA3 region after reactivation of partially acquired and old memories but not for strongly acquired and recent memories. We also demonstrated that the update of a previously stable memory required, again, a memory reconsolidation in the hippocampal CA3. Finally, we found that the reactivation of a strongly acquired memory requires an activation of the anterior cingulate cortex as soon as 24 h after acquisition. This study demonstrates the importance of the knowledge of the task on the dynamic nature of memory reconsolidation processing.
... One mass-training procedure was performed to unambiguously separate acquisition from consolidation processes. With this massed procedure, we have the same hippocampal involvement during acquisition and consolidation as found in the distributed procedure [32,33]. The procedure included one training session composed of 4 blocks, each consisting of three consecutive trials. ...
Eph receptors and their ephrin ligands play critical roles in the development of the nervous system, however, less is known about their functions in the adult brain. Here, we investigated the function of ephrinB1, an ephrinB family member that is mutated in CranioFrontoNasal Syndrome. We show that ephrinB1 deficient mice (EfnB1(Y/-) ) demonstrate spared spatial learning and memory but exhibit exclusive impairment in non-spatial learning and memory tasks. We established that ephrinB1 does not control learning and memory through direct modulation of synaptic plasticity in adults, since it is not expressed in the adult brain. Rather we show that the cortex of EfnB1(Y/-) mice displayed supernumerary neurons, with a particular increase in calretinin-positive interneurons. Further, the increased neuron number in EfnB1(Y/-) mutants correlated with shorter dendritic arborization and decreased spine densities of cortical pyramidal neurons. Our findings indicate that ephrinB1 plays an important role in cortical maturation and that its loss has deleterious consequences on selective cognitive functions in the adult.
