Looking beyond the standard version of the Morris water task in the assessment of mouse models of cognitive deficits.

Most studies investigating hippocampal dependent learning and memory in mouse models of disease use the standard version of the MWT, in which a place is learned over several days. While useful in determining if there are learning and memory deficits, often it is not clear if memory acquisition, consolidation, or retrieval is affected. For rats, we developed a variant of the task in which we added a single massed training session to a new location after the standard distributed version of the MWT. Using this version of the task, competition between these two spatial representations can then be assessed in a probe trial. We have found in rat models of Alzheimer's disease that this paradigm can detect subtle impairments that are often missed in the standard version of the MWT. To our knowledge MWT paradigms with a single massed training session have never been employed for mice. We sought to validate this paradigm for the use of assessing mouse models of disease. In the first two experiments, control mice did not have a preference for the new platform location, but instead with extensive training in the massed session displayed a preference for both the old and new locations. In the third experiment, a novel mouse model of AD was impaired in the standard version of the MWT, but not in the massed training phase of this paradigm. Importantly, these data demonstrate that our paradigm is more informative in characterizing spatial learning and memory in mouse models of disease. This article is protected by copyright. All rights reserved.