Search strategy selection in the Morris water maze indicates allocentric map formation during learning that underpins spatial memory formation

Jake Rogers, Leonid Churilov, Anthony J. Hannan, Thibault Renoir

Using a Matlab classification algorithm, we demonstrate that a highly salient distal cue array is required for significantly increased likelihoods of spatial search strategy selection during Morris water maze spatial learning. We hypothesized that increased spatial search strategy selection during spatial learning would be the key measure demonstrating the formation of an allocentric map to the escape location. Spatial memory, as indicated by quadrant preference for the area of the pool formally containing the hidden platform, was assessed as the main measure that this allocentric map had formed during spatial learning. Our C57BL/6J wild-type (WT) mice exhibit quadrant preference in the highly salient cue paradigm but not the low, corresponding with a 120% increase in the odds of a spatial search strategy selection during learning. In contrast, quadrant preference remains absent in serotonin 1A receptor (5-HT1AR) knockout (KO) mice, who exhibit impaired search strategy selection during spatial learning. Additionally, we also aimed to assess the impact of the quality of the distal cue array on the spatial learning curves of both latency to platform and path length using mixed-effect regression models and found no significant associations or interactions. In contrast, we demonstrated that the spatial learning curve for search strategy selection was absent during training in the low saliency paradigm. Therefore, we propose that allocentric search strategy selection during spatial learning is the learning parameter in mice that robustly indicates the formation of a cognitive map for the escape goal location. These results also suggest that both latency to platform and path length spatial learning curves do not discriminate between allocentric and egocentric spatial learning and do not reliably predict spatial memory formation. We also show that spatial memory, as indicated by the absolute time in the quadrant formerly containing the hidden platform alone (without reference to the other areas of the pool), was not sensitive to cue saliency or impaired in 5-HT1AR KO mice. Importantly, in the absence of a search strategy analysis, this suggests that to establish that the Morris water maze has worked (i.e. control mice have formed an allocentric map to the escape goal location), a measure of quadrant preference needs to be reported to establish spatial memory formation. This has implications for studies that claim hippocampal functioning is impaired using latency to platform or path length differences within the existing Morris water maze literature.