The Effect Of Dentate Gyrus-Specifically Overexpressed βCaMKII On Learning/Memory-Related Behavior In Mice

CaMKII (Calcium/calmodulin-dependent protein kinase II), which is composed of α and β subunits, plays an important role in synaptic plasticity and learning/memory. However, we have limited understanding about the specific roles of P CaMKII in these processes. In the βCaMKII-F90G transgenic mice, βCaMKII is overexpressed particularly in dentate gyrus (DG). By applying the transgenic mice to fear conditioning-based behavioral experiments, we studied the specific roles of P CaMKII and DG in the learning/memory-related behavior.Surprisingly, we found that the transgenic mice showed significant contextual fear memory impairment only when tested on day 10 after training, but not on day 7、day 9 or day 11. This behavioral pattern in transgenic mice hints that there may be a potential spontaneous remodeling process requires accurate CaMKII activity in DG at specific time during memory consolidation, which may underlie the transformation of memory from long term to long lasting. And this spontaneous remodeling may be related to the structural role of βCaMKII. These findings provide us new clues to study the consolidation and formation of long lasting memory.Our previous studies have demonstrated that overexpression of aCaMKII in the forebrain during reconsolidation disrupts the one-day memory after retrieval. However, up-regulating the activity of PCaMKII during the initial stage of memory reconsolidation didn’t have the same effect. Despite the different regional expression pattern, which may explain the different behavioral phenotypes of these two transgenic mouse lines, the distinct roles of βCaMKⅡ from aCaMKⅡ may also contribute to it.DG has been shown to be highly involved in pattern separation. However, in our current study using fear conditioning-based discrimination task, the transgenic mice showed comparable ability to distinguish between similar contexts with their wild type littermates. Maybe it’s because that the overexpression of PCaMKII only causes weak phenotype, which is masked by the complex discrimination task. It is also possible that the overexpression of PCaMKII doesn’t affect the function of DG in pattern separation.Overall, our studies provided more evidence to understand the roles of PCaMKII and DG in learning and memory, and also pointed out the direction for further research.