Disruption of the grid cell network in a mouse model of early Alzheimer's disease

Early-onset familial Alzheimers disease (AD) is marked by an aggressive buildup of amyloid beta (A{beta}) proteins, yet the neural circuit operations impacted during the initial stages of A{beta} pathogenesis remain elusive. Here, we report a coding impairment of the medial entorhinal cortex (MEC) grid cell network in a transgenic mouse model of familial AD that over-expresses A{beta} throughout the hippocampus and entorhinal cortex. Grid cells showed reduced spatial periodicity, spatial stability, and synchrony with interneurons and head-direction cells. In contrast, the spatial coding of non-grid cells within the MEC, and place cells within the hippocampus, remained intact. Grid cell deficits emerged at the earliest incidence of A{beta} fibril deposition and coincided with impaired spatial memory performance in a path integration task. These results demonstrate that widespread A{beta}-mediated damage to the entorhinal-hippocampal circuit results in an early impairment of the entorhinal grid cell network.