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

Early-onset familial Alzheimer's 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 the J20 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. It remains poorly understood how the onset of Alzheimer's disease affects spatial cognition. Here, the authors report that spatial coding in grid cells deteriorates over time in a mouse model of Alzheimer's disease during the early stages of pathology while place cell and head direction coding remain intact.