Failures to reconsolidate memory in a mouse model of Alzheimer’s disease

Abstract

Previous studies have demonstrated that the formation of spatial, contextual and trace conditioning memories are impaired in animal models of Alzheimer’s disease (AD), consistent with the observations that the first sign of cognitive decline in AD includes difficulties in the acquisition of new information or memory formation. Evidence is accumulating that memory retrieval is a dynamic process in which stored information becomes labile again and needs to be restabilized. However, it is poorly understood how this process referred to as memory reconsolidation is affected in animal models of AD. The present study was designed to use contextual fear conditioning to compare the changes in memory formation and subsequent reconsolidation processes in transgenic mice that overexpress human APP and PS1 harboring five familial AD mutations (5XFAD model). The results clearly demonstrate that cognitive dysfunction starts to occur primarily as reduced levels of contextual learning or memory formation in 5XFAD mice, but it is exacerbated by additional retrieval-dependent retrograde amnesia due to deficient reconsolidation as disease further develops.