Memory update and hippocampal network deficits in early Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by a significant decline in episodic memory. More recent research indicates that impairments in spatial navigation may serve as a more sensitive biomarker for AD compared to episodic memory alterations. To study the cellular mechanisms behind spatial memory and navigation deficits in AD we used the APP/PS1 mouse model of amyloidosis. To assess spatial memory updating, a non-stressful paradigm called Objects in Updated Locations (OUL) was employed. This task allows the quantification of the different times of exploration of the familiar, novel or updated object locations in an open field arena. We tested mice at 7-9 months and 10-11 months. Our data indicates that only 10-11 months APP/PS1 mice show a reduced exploration of novel locations, indicating a deficit in memory formation. Previous studies from our lab have pointed to changes in theta phase precession being correlated with spatial memory deficits. In order to understand changes in network function that may underlie the OUL behavior phenotype, we recorded local field potentials before, during, and after APP/PS1 mice ran on a 1.5m linear track. In local field potential recordings from CA1, we assessed the differences in power and frequency of theta oscillations (during running periods) and sharp wave ripples (during rest periods). We further examined single-cell activity in the linear track. This research contributes to a better understanding of memory circuit deficits in AD, offering insights that may lead to potential therapeutic strategies for the condition.