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Authors & Affiliations
Shreya Bangera, Patrick Honma, Reuben Thomas, Dan Xia, Jorge Palop
Abstract
The ability to learn and adapt to cognitive demands is vital for survival, and mice serve as valuable models in neuroscience for studying these processes. In this study, we introduce a novel maze framework to investigate learning and adaptability in mice, specifically focusing on humanized App knock-in models of Alzheimer's disease. The maze mimics decision-making scenarios, similar to when foraging, with an optimal reward path leading to a target with sucrose pellets. Decision nodes introduce off-reward routes to dead-ends or loops, creating a challenge requiring mice to balance exploration with goal-oriented behavior. The study involved a 13-hour overnight trial using both Wild-type (WT) and AppSAA knock-in Alzheimer’s mice. Over time, mice displayed increased preference for the target zone, but AppSAA mice exhibited significant impairments, including spending less time at the target, more frequent deviations to off-reward paths, and taking longer routes to the target. We developed a hierarchical probabilistic framework to analyze spatial learning and decision-making in the maze, influenced by non-local cues and reward anticipation. The first level employs a discrete-time Hidden Markov Model (HMM) to capture navigational states, reflecting motor actions and movement strategies. The second level combines a Bayesian Gaussian Mixture Model (BGMM) and a Gaussian Mixture Model HMM (GMM-HMM), incorporating spatial data and inferred patterns to capture the temporal evolution of reward-oriented strategies. This approach provides a detailed view of fine-scale behavioral dynamics and the development of goal-directed navigation, revealing the cognitive mechanisms driving decision-making. The maze was enhanced with timed rewards and simultaneous electrophysiological recordings, enabling multi-modal analysis linking behavior to neural activity. This framework uncovers how specific brain dynamics support cognitive flexibility and learning, offering insights into the neural basis of decision-making during complex navigation.