Translating the Human CANTAB Touchscreen Based Tasks to Evaluate Learning and Memory in Mouse Models of Down Syndrome

Abstract

Humans with Down syndrome (DS) exhibit hippocampal learning deficits in the Cambridge Neuropsychological Test Automated Battery (CANTAB). Here we translated the CANTAB Visual Discrimination (VD) and Extinction tasks to investigate hippocampal learning and cortical inhibitory control in the Dp(16)1/Yey, Ts65Dn and Ts1Cje mouse models of DS. No food or water restriction was used prior to testing. The number of days to reach 70% correct answers and percent of correct responses were analyzed. All Dp(16)1/Yey, Ts1Cje and WT mice reached Stage 5 of pre-training. No differences between genotypes were found in percent of correct responses. Five Ts65Dn and one WT animals reached Stage 5 and only one Ts65Dn mouse reached VD. Ts1Cje mice took longer (17.86{+/-}3.19 days) to move to VD vs. WT (11.44{+/-}1.96 days, P=0.09). There were no differences between Dp(16)1/Yey and WT mice. At VD, the average percent of correct answers was significantly lower in Dp(16)1/Yey (22.70{+/-}1.93%) and Ts1Cje (34.39{+/-}1.98%) compared to WT littermates (32.18{+/-}1.49% and 41.11{+/-}1.45%, respectively, P<0.05). In another set of experiments, we demonstrated that mild food restriction significantly reduced the time needed to complete pre-training in C57BL/6J mice compared to C67BL/6J mice that had ad libitum access to food and water. In conclusion, we were able to apply human cognitive tests to evaluate hippocampal learning and cortical inhibitory control in three mouse models of DS. These studies demonstrate significant cognitive differences between strains. Future experiments will evaluate whether food restriction and/or pre- and postnatal therapy decreases the time intervals to achieve training mile.