Search strategies used by APP transgenic mice during navigation in the Morris water maze.

TgCRND8 mice represent a transgenic mouse model of Alzheimer's disease, with onset of cognitive impairment and increasing amyloid-beta plaques in their brains at 12 weeks of age. In this study, the spatial memory in 25- to 30-week-old TgCRND8 mice was analyzed in two reference and one working memory Morris water maze (MWM) tests. In reference memory tests, the mice were trained to escape to a hidden platform, which in one version of the test was marked by a visual cue. In the working memory test, the hidden platform was moved daily to different locations. The TgCRND8 mice were impaired in reference memory when trained in a hidden platform test. However, the mice developed spatial memory comparable to non-Tg littermates in a cued reference memory test. The mice showed also an impairment in spatial working memory. Analysis of search paths revealed that in contrast to non-Tg littermates, TgCRND8 mice did not use spatial strategies during their navigation. Instead, they learned to locate an escape platform using a nonspatial, chaining strategy. The study showed that (1) the impairment in the reference memory of TgCRND8 mice was reduced when a hidden platform was cued, and that (2) both working and reference memory systems of TgCRND8 mice, but not (3) the plasticity of choice between search strategies, are compromised by the transgene-induced pathology.