Reactivation with a simple exposure to the experimental environment is sufficient to induce reconsolidation requiring protein synthesis in the hippocampal CA3 region in mice

Abstract

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 experimental reactivation procedure. Here, we addressed the question of whether protein synthesis in the CA3 hippocampal region is crucial in memory consolidation and reconsolidation of allocentric knowledge after reactivation in different experimental conditions in the Morris water maze. We showed (1) that an injection of the protein synthesis inhibitor anisomycin in the CA3 region during consolidation or after a single reactivation trial disrupted performance and (2) that protein synthesis is required even after a simple contextual reactivation without any learning trial and independently of the presence of the reinforcement. This work demonstrates that a simple exposure to the spatial environment is sufficient to reactivate the memory trace, to make it labile, and that reconsolidation of this trace requires de novo protein synthesis.

Intrahippocampal infusions of anisomycin produce amnesia: Contribution of increased release of norepinephrine, dopamine, and acetylcholine

“…These findings are consistent with those of many prior studies involving injections of protein synthesis inhibitors into the hippocampus (e.g., Bourtchouladze et al 1998;Quevedo et al 1999Quevedo et al , 2004Taubenfeld et al 2001;Barriantos et al 2002;Agnihotri et al 2004;Artinian et al 2007), as well as into other brain areas such as the amygdala (Nader et al 2000;Schafe and LeDoux 2000;Debiec et al 2002;Duvarci et al 2005;Parsons et al 2006;Milekic et al 2007), and prefrontal cortex (Santini et al 2004;Akirav and Maroun 2006;Touzani et al 2007). These reports are part of a large set of papers showing that direct brain injections of protein synthesis inhibitors produce amnesia for many tasks (cf.…”

Characterization of spatial memory reconsolidation

“…Morris et al (2006) showed that inactivation of the dorsal hippocampus during reconsolidation by anisomycin (a protein synthesis inhibitor) has no effect on the MWM performances. However, in previous studies (Artinian et al 2007(Artinian et al , 2008, we showed that the hippocampal CA3 region is crucial for reconsolidation of spatial information in this same task. Different factors could explain this apparent discrepancy, but the most important fact is that, unlike us, Morris et al (2006) used a distributed learning procedure leading to an asymptotic level of performances before the reactivation trial.…”

“…They were tested during the first half of the light period. The strain of mice was chosen for their very good performances in spatial memory (Artinian et al 2007(Artinian et al , 2008. Moreover, CD1 mice exhibit a high endurance that is necessary in a massed procedure in the MWM.…”

“…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.…”

“…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.…”