A behavioural assay for investigating cued conflict between allocentric and egocentric spatial memory with instinctive escape in mice

Instinctive escape behavior is widely recognized as a reliable model for assessing spatial memory in mice. Here, we present a novel behavioral assay designed to evaluate how mice navigate toward a learned goal relying on a variable proximal LED landmark or internal egocentric cues to provide spatial orientation in the absence of distal cues. Escape to a learned shelter was triggered by an innately aversive auditory stimulus in the presence of a proximal LED landmark. To assess cue preference (egocentric vs. allocentric), we introduced a cue-conflict situation where the allocentric LED cue was deliberately shifted away from the previously visited shelter location. In a no-conflict scenario, the LED stayed directly above the shelter. Baseline tests in C57BL/6 J mice showed a decreased reliance on allocentric cues as the LED landmark deviated further from the actual shelter. When the disparity between the LED cue and the shelter location exceeded a threshold, the mice began to favor egocentric strategies over allocentric ones. To demonstrate its utility, we applied the cue-conflict assay in a cross-sectional study of the 5xFAD Alzheimer's disease (AD) mouse model at early pathological stages (2-3 months of age). Escape profiles in AD and wild-type (WT) mice revealed a complex, genotype-dependent pattern of behavior across LED shift conditions, independent of disease progression. Although both AD and WT mice exhibited a higher incidence of allocentric (LED-directed) escapes when the LED shift was small, our analysis did not reveal significant changes in escape strategy that were associated with condition, genotype or age. Future studies using neural recording and manipulation techniques can further elucidate the circuit-level mechanisms underlying the cue conflict resolution.