Aberrant medial entorhinal cortex dynamics link tau pathology to spatial memory impairment.

ABSTRACT: Tau pathology in the entorhinal cortex (EC) is associated with spatial memory decline in aging and early-stage Alzheimer's disease, but its impact on EC computations during learning is not well understood. We performed longitudinal two-photon calcium imaging of layer 2 excitatory neurons in the medial EC (MEC) of PS19 tauopathy mice over 10 days of an operant spatial learning task. Male PS19 mice showed marked learning impairments accompanied by dysregulated MEC activity and unstable spatial coding. Their activity also showed weakened representations in cue-poor relative to cue-rich regions, correlated with attenuated speed modulation. These changes suggest that impaired path integration destabilizes MEC spatial maps, leading to impaired spatial memory. In contrast, female PS19 mice exhibi

SUBMITTER: Malone TJ 

PROVIDER: S-EPMC12776407 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature