Rescuing impaired hippocampal-cortical interactions and spatial reorientation learning and memory during sleep in a mouse model of Alzheimer’s disease using hippocampal 40 Hz stimulation

In preclinical Alzheimer's disease (AD), spatial learning and memory is impaired. We reported similar impairments in 3xTg-AD mice on a virtual maze (VM) spatial-reorientation-task that requires using landmarks to navigate. Hippocampal (HPC)-cortical dysfunction during sleep (important for memory consolidation) is a potential mechanism for memory impairments in AD. We previously found deficits in HPC-cortical coordination during sleep coinciding with VM impairments the next day. Some forms of 40 Hz stimulation seem to clear AD pathology in mice, and improve functional connectivity in AD patients. Thus, we implanted a recording array targeting parietal cortex (PC) and HPC to assess HPC-PC coordination, and an optical fiber targeting HPC for 40 Hz or sham optogenetic stimulation in 3xTg/PV