MEET QPS AT AD/PD™ 2024; March 5-9, Lisbon, Portugal

Search Strategy Analysis Details Morris Water Maze Readouts

QPS Neuropharmacology

We now offer advanced search strategy analysis of data gathered during Morris Water Maze (MWM) test without changes to the established protocol. The MWM has been a widely recognized method to analyze spatial navigation and learning for several decades. This makes it a valuable tool for the evaluation of cognitively impaired rodent models, used to study e. g. Alzheimer’s disease. The conventional readouts of the MWM, such as latency to find the hidden platform or distance traveled, are not designed to capture complex behavioral differences. To make optimal use of this valuable test, we established an additional analysis method to categorize the path traversed into different search strategies and associated them with a cognitive score (Figure 1A) based on a previously published and peer-reviewed algorithm (Cooke et al., 2020 & Curdt et al., 2022). This additional information can shed further light on cognitive deficits and is proven to be more sensitive than the conventional analysis method (Figure 1 A vs. B, C). The cognitive score can be a valuable initial metric to evaluate the learning progress between trainings trials.

Figure 1-Pathfinder

Figure 1: Cognitive score of the analysis of strategy compared with the latency to escape of the conventional analysis. Assessment of spatial learning in 5xFAD mice and non-transgenic (ntg) littermates during training days 1-4 and probe trial (PT). (A) Categorization and grading of search strategy with a higher score indicating the usage of more spatial memory-dependent strategies. (B-C) Conventional MWM analysis, evaluating the latency to escape during training and target zone crossings during the probe trial (PT). Two-way ANOVA followed by Bonferroni’s multiple comparisons post hoc test (A, B); Mann-Whitney test (C); mean ± SEM; n = 24 per group; mixed sex; *p<0.05, **p<0.01.

In addition to the cognitive score, search strategy analysis can provide an easy-to-understand graph to further elucidate nuances of spatial learning by depicting the different strategies used at each training day and the probe trial (PT). By highlighting the more spatial learning and hippocampus-dependent strategies in blue while showing the low memory-dependent strategies in red, the progress over time can be attractively visualized. For statistical analysis, the amount of hippocampus-dependent compared to hippocampus-independent strategies at each day can be compared to non-transgenic (ntg) littermates (Figure 2A). Compared to readouts of the conventional analysis approach, this evaluation adds significant value to the existing data.

Figure 2-Pathfinder

Figure 2: Strategy overview compared to distance moved and thigmotaxis metrics of the conventional analysis method. Assessment of spatial learning in 5xFAD mice and ntg littermates during training days 1-4 and PT. (A) Bar graph in percent of strategies used per day. Red indicates hippocampus-independent search strategies while blue are hippocampus-dependent search strategies. Statistical analysis was performed by comparing the percent of dependent vs independent search strategies per day of 5xFAD mice and ntg littermates. (B) Distance travelled and thigmotaxis of conventional analysis. Two-way ANOVA followed by Bonferroni’s multiple comparisons post hoc test; mean ± SEM; n = 24 per group; mixed sex; *p<0.05, **p<0.01, ***p<0.001.

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