Calcium/calmodulin-dependent kinase II and memory destabilization: a new role in memory maintenance.

Fabio Antonio Vigil,Karl Peter Giese

doi:10.1111/jnc.14454

Abstract

In this review, we discuss the poorly explored role of calcium/calmodulin‐dependent protein kinase II (CaMKII) in memory maintenance, and its influence on memory destabilization. After a brief review on CaMKII and memory destabilization, we present critical pieces of evidence suggesting that CaMKII activity increases retrieval‐induced memory destabilization. We then proceed to propose two potential molecular pathways to explain the association between CaMKII activation and increased memory destabilization. This review will pinpoint gaps in our knowledge and discuss some ‘controversial’ observations, establishing the basis for new experiments on the role of CaMKII in memory reconsolidation. The role of CaMKII in memory destabilization is of great clinical relevance. Still, because of the lack of scientific literature on the subject, more basic science research is necessary to pursue this pathway as a clinical tool.

Highlights

Due to its ability to switch from a CaM-dependent to a CaM-independent state of activation by threonine 286 (T286)/287 autophosphorylation, calmodulindependent protein kinase II (CaMKII) has been suggested to act as a memory molecule, preserving “memories” of strong calcium signals (Lisman 1994)
T286A mutant mice lack the ability to autophosphorylate at the T286 site, and have one of the most severe spatial learning deficits described in a mutant mouse (Giese et al 1998, Need & Giese 2003)
The role of CaMKII in memory maintenance has always been a matter of debate (Lisman 1994, Sanhueza & Lisman 2013, Buard et al 2010, Irvine et al 2005, Lucchesi et al 2011, Rossetti et al 2017)

Summary

Conclusion

The role of CaMKII in memory maintenance has always been a matter of debate (Lisman 1994, Sanhueza & Lisman 2013, Buard et al 2010, Irvine et al 2005, Lucchesi et al 2011, Rossetti et al 2017). Da Silva et al (2013) observed that hippocampal CaMKII inhibition by AIP after spatial memory retrieval induces memory impairment, which was rescued by inhibiting protein degradation. This memory impairment phenotype was time-dependent, not present 24 hours after AIP treatment but present 5 days after. CaMKII plays a role in memory maintenance, not as a “memory molecule”, but rather as biological substrate of memory reconsolidation If this is the case, understanding how CaMKII regulates retrieval-induced memory destabilization could have an enormous impact on the treatment of post-traumatic stress disorder and addiction. Investigating the role of CaMKII in different brain areas, as well as the effect of CaMKII manipulation at different time points after the process of learning and retrieval will require a collaborative, long and challenging effort from many researchers

CaMKII manipulation

Pharmacological blocking of CaMKII with