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Long-term storage of information into memory is supposed to rely on long-term synaptic plasticity processes. Detection of such synaptic changes after training in long-term or reference memory (RM) tasks has yet been scarce, variable and only studied on a short time scale. On the other hand, short-term or working memory (WM) is largely known to depend on persistent neuronal activity or short-term plasticity processes. However, processing information into WM could also involve long-term synaptic changes that could be responsible for the erasure/forgetting of items previously stored in WM playing the role of proactive interference. In order to study long-term synaptic changes associated with RM or WM, we trained chronically implanted rats in three different radial maze tasks: a classical RM task and two WM tasks involving different levels of proactive interference. Synaptic responses at the perforant path to dentate gyrus synapse were recorded on a long-time scale (24h) in freely-moving rats after training in one of these three tasks. We found that consolidation of long-term information leads to a delayed synaptic potentiation, occurring 9 hours after RM training and predicting good behavioral performance on the following day. In contrast, optimal information processing into WM triggers a synaptic depression immediately observed after training and lasting 3 hours, that could act as a mechanism for interference erasure/forgetting.

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Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference. To determine the role of CaMKII and GluA1 in adaptive forgetting, we adopted a comparative approach to assess the relative quantity and phosphorylation state of these proteins in the brain of rats trained in one of three radial maze paradigms: a RM task, a WM task involving a high level of adaptive forgetting, or a WM involving a low level of adaptive forgetting. Surprisingly, Western blot analyses revealed that training in a WM task involving a high level of adaptive forgetting specifically increased the expression of AMPA receptor GluA1 subunit and the activity of CaMKII in the dentate gyrus. These results highlight that WM with proactive interference involves mechanisms of synaptic plasticity selectively in the dentate gyrus.

Prolonged rapid-eye-movement (REM) sleep deprivation has long been used to study the role of REM sleep in learning and memory processes. However, this method potentially induces stress and fatigue that may directly affect cognitive functions. Here, by using a short-term and nonstressful REM sleep deprivation (RSD) method we assessed in rats the bidirectional influence of reduced and increased REM sleep amount on hippocampal-dependent emotional memory and plasticity. Our results indicate that 4 h RSD impaired consolidation of contextual fear conditioning (CFC) and induction of long-term potentiation (LTP), while decreasing density of Egr1/Zif268-expressing neurons in the CA1 region of the dorsal hippocampus. LTP and Egr1 expression were not affected in ventral CA1. Conversely, an increase in REM sleep restores and further facilitates CFC consolidation and LTP induction, and also increases Egr1 expression in dorsal CA1. Moreover, CFC consolidation, Egr1 neuron density, and LTP amplitude in dorsal CA1 show a positive correlation with REM sleep amount. Altogether, these results indicate that mild changes in REM sleep amount bidirectionally affect memory and synaptic plasticity mechanisms occurring in the CA1 area of the dorsal hippocampus.

How does the brain discriminate essential information aimed to be stored permanently from information required only temporarily, and that needs to be cleared away for not saturating our precious memory space? Reference Memory (RM) refers to the long-term storage of invariable information whereas Working Memory (WM) depends on the short-term storage of trial-unique information. Previous work has revealed that WM tasks are very sensitive to proactive interference. In order to prevent such interference, irrelevant old memories must be forgotten to give new ones the opportunity to be stabilized. However, unlike memory, physiological processes underlying this adaptive form of forgetting are still poorly understood. Here, we precisely ask what specific brain structure(s) could be responsible for such process to occur. To answer this question, we trained rats in a radial maze using three paradigms, a RM task and two WM tasks involving or not the processing of interference but strictly identical in terms of locomotion or motivation. We showed that an inhibition of the expression of Zif268 and c-Fos, two indirect markers of neuronal activity and synaptic plasticity, was observed in the dentate gyrus of the dorsal hippocampus when processing such interfering previously stored information. Conversely, we showed that inactivating the dentate gyrus impairs both RM and WM, but improves the processing of interference. Altogether, these results strongly suggest for the first time that the dentate gyrus could be a key structure involved in adaptive forgetting.

Study objectives It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. Methods We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. Results We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. Conclusions These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM.

De toutes les fonctions possibles qui ont pu etre attribuees au sommeil, son influence sur la memoire est certainement l’une des plus etudiee. Un certain nombre de travaux suggere ainsi que le sommeil pourrait faciliter la consolidation d’information en memoire, alors que d’autres suggerent qu’il participerait a l’oubli d’informations. En effet, l’oubli n’a pas toujours les fonctions deleteres qu’on lui donne generalement. Il pourrait avoir un role adaptatif en permettant la mise a l’ecart d’informations peu importantes encodees tout au long d’une journee. Le sommeil favoriserait donc la memoire en permettant l’effacement selectif des traces mnesiques inutiles pour laisser place aux informations les plus pertinentes. Des travaux de notre equipe ont montre que l’oubli d’informations requiert la diminution a long terme (LTD) de l’efficacite synaptique. Les frequences necessaires pour induire artificiellement la LTD etant proches de celle observees pendant le sommeil a onde lente, l’oubli d’informations non pertinentes pourrait donc avoir lieu pendant le sommeil lent ; le renforcement des informations plus essentielles au sujet ayant lieu pendant l’autre phase du sommeil, le sommeil paradoxal. Nous avons teste cette hypothese en etudiant le sommeil de rats prealablement entraines dans des tâches mettant en jeux soit (1) la memoire de reference qui necessite le stockage a long terme d’une information invariante, soit (2) la memoire de travail (MT) a haut niveau d’interferences, qui requiert la memorisation a court terme d’une information variable mais aussi l’oubli l’information prealablement stockees, soit (3) la MT avec un faible niveau d’interference pendant laquelle l’oubli n’est pas necessaire. Nous avons aussi teste l’effet de privations de sommeil total (ou paradoxal) sur les performances de rats entraines dans ces tâches. Si ces etudes montrent effectivement un role du sommeil paradoxal dans la consolidation et un role du sommeil lent dans l’oubli, il semble que les phenomenes oscillatoires courts au sein de ces episodes (ripples, spindles et theta rapide) aient des roles beaucoup plus contrastes. Informations complementaires Travail finance par la Regions Rhone Alpes (ARC-2 bien-etre et vieillissement).