The Effect Of CaMKⅡα On Long-term Memory Reconsolidation

It is well accepted that, acqusition, consolidation, storage and retrieval are four main stages of memory processes. However, when the stable memory is reactivated, it will enter a labile state from which the memory must be re-stabilized during a process known as reconsolidation. Therefore, memory reconsolidation is also considered an important part of the long-term memory dynamic process.At present, many studies have found that memory reconsolidation, is not a simple replication of memory consolidation, and has a unique molecular mechanism. Using aCaMKII-F89G transgenic mice, we investigated the effects of CaMKⅡα in memory reconsolidation by regulating the activity of aCaMKII in both temporal and regional manner. We found that, the post-reactivated long-term memory was disrupted with the elevation of aCaMKII-F89G activity immediately after retrieval, whereas the post-reactivated short-term memory still remained intact. Moreover, we demonstrated that there is a critical time window for the involvement of CaMKIIa in the process of reconsolidation. The post-reactivated long-term memory would only be disrupted if aCaMKII-F89G activity was up-regulated during the initial 10 minutes after memory retrieval. Not only we found that only the reactivated memory was liable to be disrupted, but also there was no spontaneous recovery for the disrupted memory two weeks after memory retrieval. Finally, we showed that both NMDAR and proteasome inhibitors can abolish the devastated effect of up-regulation of aCaMKII-F89G activity during reconsolidationIn conclusion, CaMKIIa plays an important role in memory reconsolidation. Upon retrieval of long-term memory, the NMDA receptor is activated. With the elevation of Ca2+ through NMDAR, CaMKⅡα can be activated via binding Ca2+/calmodulin. The activated CaMKIIa thus translocate proteasome to dendritic spines and trigger protein degradation. The process of protein degradation may serve as an important initial step for memory remodel and recombination during reconsolidation.