049 Hippocampal place cell dysfunction in an APP knock-in mouse model of Alzheimers disease

The hippocampus is one of the first cortical regions to exhibit Alzheimer’s disease (AD) pathology. The spatially-related firing of hippocampal place cells provides the cellular basis for spatial memory, and although this is impaired relatively early in AD few studies have examined the effects of AD pathology on place cell firing.

An in-depth characterisation of hippocampal pyramidal cell activity was undertaken in an APP knock-in model. Electrophysiological recordings from the left CA1 subregion of four 15-month-old, freely moving, APPNL-G-F mice and four wild-type littermate controls yielded data from 270 cells. Following recordings amyloid β plaque burden was quantified in fixed sections of APPNL-G-F brain tissue stained with Thioflavin-S.

Significantly fewer APPNL-G-F pyramidal cells exhibited spatial firing, and APPNL-G-F place cells showed deficits in rate coding and temporal coding of spatial information. APPNL-G-F place cells had a lower spatial information content, larger place fields, reduced phase-locking to the theta rhythm of the local field potential, and a reduction in theta phase precession. A positive correlation was identified between amyloid β plaque burden and pyramidal cell spatial information.

The results provide initial support for the hypothesis that AD pathology disrupts hippocampal function which manifests as altered place cell activity and spatial behaviour.