Disrupted Place Cell Remapping and Impaired Grid Cells in a Knockin Model of Alzheimer's Disease

Patients with Alzheimer's disease (AD) suffer from spatial memory impairment and wandering behavior, but the brain circuit mechanisms causing such symptoms remain largely unclear. In healthy brains, spatially tuned hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments, a circuit function called “remapping.” We tested remapping in amyloid precursor protein knockin (APP-KI) mice with impaired spatial memory. CA1 neurons, including place cells, showed disrupted remapping, although their spatial tuning was only mildly diminished. Medial entorhinal cortex (MEC) neurons severely lost their spatial tuning and grid cells were almost absent. Fast gamma oscillatory coupling between the MEC and CA1 was also impaired. Mild disruption of MEC grid cells emerged in younger APP-KI mice, although the spatial memory and CA1 remapping of the animals remained intact. These results point to remapping impairment in the hippocampus, possibly linked to grid cell disruption, as circuit mechanisms underlying spatial memory impairment in AD. [Display omitted] •Remapping of place and grid cells was investigated in APP knockin mice•Place cells were mildly deteriorated but showed severely disrupted remapping•Grid cells were severely impaired, leaving few neurons with the ability to remap•Disruption of grid cells, but not place cells, emerged in younger APP knockin mice Place cells in the hippocampus exhibit distinct spike patterns in different environments, a circuit function called remapping. Jun et al. show that remapping is disrupted in the APP knockin mouse model, suggesting that remapping impairment is a circuit mechanism underlying spatial memory impairment in Alzheimer's disease.