Synaptic reentry reinforcement based network model for long‐term memory consolidation

Abstract

ABSTRACT:The conversion of newly formed declarative memories into long-term memories is known to be dependent on the hippocampus. Recent experiments suggest that memory consolidation requires reactivation of the NMDA receptor in CA1 during the initial week(s) after training. This led to the hypothesis that the repeated post-learning reinforcement of synaptic modifications, termed synaptic reentry reinforcement (SRR), is essential for long-term memory consolidation and storage. Based on experimental observations, we have built a computational model to further illustrate and explore the effect of the SRR process on the formation of long-term memory. We show that SRR is capable of strengthening and maintaining memory traces despite inherent variability in the system due to such processes as the turnover of synaptic receptors and their associated signaling and structural proteins. Furthermore, we demonstrate that new rounds of synaptic modification triggered by memory reactivation, either during conscious recall or sleep, could lead to the selective consolidation of a subset of memory traces. Finally, we show why the SRR process in the hippocampus is required during the initial post-training weeks for synaptic reinforcement based memory consolidation in the cortex. Hippocampus 2002;12:637-647.

Networks of neurons, networks of genes: An integrated view of memory consolidation

“…This second element in the PTM model (p. 16, 2 nd paragraph in the original publication) describes the metastability of memory networks and suggests "that change underlying memory storage is never stable at the level of an individual synapse". This view is similar to ours (Figure 1) and that of others in the field, who suggest a greater degree of dynamics in the synaptic nature of memory traces (Abraham & Robins, 2005;Gold, 2006;Wittenberg, Sullivan, & Tsien, 2002).…”

Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain

“…Inducible gene knockout experiments show that the formation of long-lasting memories is severely disrupted if the NMDA receptor in the CA1 region of the hippocampus is selectively and inducibly knocked out during the initial posttraining week(s) (1). This finding suggests that memory consolidation requires multiple rounds of postlearning synaptic modifications to reinforce synaptic changes initiated during memory acquisition (16,17). More recently, computational analysis shows that SRR is capable of counteracting the turnover of synaptic receptors and making memory traces stronger and more stable, thus leading to memory consolidation (16,17).…”

“…More recently, computational analysis shows that SRR is capable of counteracting the turnover of synaptic receptors and making memory traces stronger and more stable, thus leading to memory consolidation (16,17). It further shows that SRR can serve as a crucial mechanism for transferring the newly created memories from the hippocampus to the cortex for permanent storage (16,17).␣-Ca 2ϩ ͞calmodulin-dependent protein kinase II (␣CaMKII) is a major downstream molecule in the NMDA receptor signaling process (18-23) and crucial for learning behaviors (24-27). However, fundamental questions still remain regarding whether and when CaMKII participates in memory consolidation process.…”

Mécanismes de consolidation de la mémoire

“…Selon les théories actuelles, la stabilisation et la conservation des souvenirs seraient tributaires d'une interaction temporaire entre la formation hippocampique et différentes régions corticales dépositai-res des souvenirs [2][3][4][5]. Au cours de ce dialogue, l'hippocampe serait capable, grâce à ses fortes capacités associatives, de réactiver, au cours de périodes dites off-line -de repos ou de sommeil -, les différents modules néocorticaux qui ont participé à l'encodage de l'information [6,7]. La récurrence de ces réactivations conduirait à la modification progressive de l'architecture du réseau néocortical par le renforcement des connexions cortico-corticales existantes ou par la créa-tion de nouvelles connexions synaptiques [8], assurant ainsi le stockage d'une trace mnésique stable et durable au niveau néocortical.…”