Disrupted remapping of place cells and grid cells in knock-in model of Alzheimer\'s disease

Patients with Alzheimer9s disease (AD) frequently suffer from spatial memory impairment and wandering behavior, but brain circuits causing such symptoms remain largely unclear. In healthy brains, spatially-tuned hippocampal place cells and entorhinal grid cells represent distinct spike patterns in different environments, a circuit function called "remapping" that underlies pattern separation of spatial memory. We investigated whether a knock-in manipulation to mutated amyloid precursor protein affects the remapping of place cells and grid cells. We found that the remapping of hippocampal place cells was severely disrupted although their spatial tuning was only mildly diminished. Entorhinal grid cells were severely impaired, sending disrupted remapping signals to the hippocampus. These results point to the link between grid cell impairment and remapping disruption as a circuit mechanism causing spatial memory impairment in AD.