Impairments in Spatial Representations of Place Cells and Neural rhythms In APP knock-in rat model.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that severely impacts spatial memory. Place cells in the hippocampus play an important role in spatial memory. However, neuronal activity in the hippocampus is difficult to monitor and study in human AD patients. Thus, it is critical to have an animal model that resembles closely human AD. The newly developed APPrat model, which is a knock-in rat line of the amyloid precursor protein (APP) with Swedish-Beyreuther/Iberian-Arctic mutations, presents a unique opportunity. In this study, we investigated how hippocampal place cells and neural rhythms were impaired in APP rats. Place cells of APP rats showed a less defined spatial tunning and disrupted remapping. In addition, APP rats exhibited decreased power of theta rhythm and slow gamma rhythm. These results suggest that the impairment of spatial memory in APP rats may be caused by the damage of place cells' ability to represent spatial location and abnormal neural rhythm in the hippocampus.