Impairment of spatial memory consolidation in APP751SL mice results in cue-guided response

APP(751SL) mice of 5-6- and 7-8-month-old and their wild-type littermates were submitted to one-session learning in a water-maze with three levels of training (4, 12 or 22 trials). Training consisted in finding a submerged platform with a fixed location and marked by a cue. During testing two platforms were presented: one consistent with the spatial location allowing place-response (PR) and the other signaled by the cue enabling cued-response (CR). When testing occurred 24 h after training, wild-type and 5-6-month-old APP(751SL) mice exhibited a shift in response strategy as a function of training level, by executing CR when trained with 4 trials and PR when trained with 12 trials, but 7-8-monthold APP(751SL) mice executed only CR. However, they displayed PR when tested 1 h after 12- and 22-trial, suggesting a consolidation deficit. Zif268 imaging showed plasticity impairment of the hippocampal-dependent memory system but not of the dorsolateral caudate nucleus. Moreover, in these APP(751SL) mice, the deficit selectively affecting hippocampal function cannot be directly related to the onset of beta-amyloid deposits. (C) 2007 Elsevier Inc. All rights reserved.