Protein degradation, as with protein synthesis, is required during not only long‐term spatial memory consolidation but also reconsolidation

Abstract

The formation of long-term memory requires protein synthesis, particularly during initial memory consolidation. This process also seems to be dependant upon protein degradation, particularly degradation by the ubiquitin-proteasome system. The aim of this study was to investigate the temporal requirement of protein synthesis and degradation during the initial consolidation of allocentric spatial learning. As memory returns to a labile state during reactivation, we also focus on the role of protein synthesis and degradation during memory reconsolidation of this spatial learning. Male CD1 mice were submitted to massed training in the spatial version of the Morris water maze. At various time intervals after initial acquisition or after a reactivation trial taking place 24 h after acquisition, mice received an injection of either the protein synthesis inhibitor anisomycin or the protein degradation inhibitor lactacystin. This injection was performed into the hippocampal CA3 region, which is specifically implicated in the processing of spatial information. Results show that, in the CA3 hippocampal region, consolidation of an allocentric spatial learning task requires two waves of protein synthesis taking place immediately and 4 h after acquisition, whereas reconsolidation requires only the first wave. However, for protein degradation, both consolidation and reconsolidation require only one wave, taking place immediately after acquisition or reactivation, respectively. These findings suggest that protein degradation is a key step for memory reconsolidation, as for consolidation. Moreover, as protein synthesis-dependent reconsolidation occurred faster than consolidation, reconsolidation did not consist of a simple repetition of the initial consolidation.

Characterization of spatial memory reconsolidation

“…First, we replicated the experiment in the Morris water maze with a simple massed acquisition procedure with reactivation ( Fig. 1C; see Materials and Methods, Experiment 1; Artinian et al 2008) or without reactivation ( Fig. 1E; see Materials and Methods, Experiment 2).…”

“…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.…”

“…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.…”

“…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.…”

The ubiquitin-proteasome pathway and synaptic plasticity

“…For example, infusion of the proteasome inhibitor b-lactone into the CA1 region of the hippocampus prevents extinction of contextual fear memory . Also, in using infusion of lactacystin into the CA3 region of the hippocampus it was shown that protein degradation is important for consolidation as well as reconsolidation of spatial memory (Artinian et al 2008). The mechanistic details as to how the UPP contributes to the extinction of fear memory or reconsolidation of spatial memory are not clearly understood.…”