Disruption of hippocampal-prefrontal neural dynamics and risky decision-making in a mouse model of Alzheimer's disease.

ABSTRACT: This study investigates how amyloid pathology influences hippocampal-prefrontal neural dynamics and decision-making in Alzheimer's disease (AD) using 5XFAD mice, a well-established model system characterized by pronounced early amyloid pathology. Utilizing ecologically relevant "approach food-avoid predator" foraging tasks, we show that 5XFAD mice exhibit persistent risk-taking behaviors and reduced adaptability to changing threat conditions, indicative of impaired decision-making. Multi-regional neural recordings reveal rigid hippocampal CA1 place cell fields, decreased sharp-wave ripple (SWR) frequencies, and disrupted medial prefrontal-hippocampal connectivity, all of which correspond with deficits in behavioral flexibility during spatial risk scenarios. These findings highlight the cri

SUBMITTER: Kim EJ 

PROVIDER: S-EPMC12451995 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature