Apolipoprotein E knockout mice display procedural deficits in the Morris water maze: analysis of learning strategies in three versions of the task

Abstract

Apolipoprotein E knockout (apoEKO) mice have been shown to be impaired in the spatial Morris water maze (MWM). However, several groups failed to replicate this finding. One reason for this inconsistency may stem from variations in the experimental protocols and environment between laboratories. In the present study, we have tested if age and variations in protocol implementation that specifically affect salience of the visual extramaze cues influence performance and navigational strategies in the MWM. We tested three- and 12-month-old apoEKO and wild type mice in three versions of the MWM differing on the availability of visual extramaze cues: (1) salient cues, (2) diffuse cues, and (3) absence of cues. Our results show that the presence of salient cues enhances acquisition performance of wild type, but not apoEKO mice in the MWM. This effect was restricted to the acquisition phase since apoEKO mice reached a level of performance that was comparable to that of controls toward the end of the task. No significant differences were detected between apoEKO and controls in either the diffuse cues or absence of cues paradigms. Thigmotaxic tendencies were observed in apoEKO mice and correlated high latency scores. Thigmotaxis may have interfered with the initial ability to engage in a proficient navigational strategy. These findings suggest that, in contrast to what has been proposed in the past, apoEKO mice appear not to be impaired in spatial memory per se but are deficient in a procedural component of the MWM. Furthermore, the procedural deficit and corresponding thigmotaxic tendencies of apoEKO mice appeared to increase with age. Taken together, these findings confirm our hypothesis that age and variations in experimental protocols can influence MWM performances.