40 Hz sensory stimulation enhances CA3–CA1 coordination and prospective coding during navigation in a mouse model of Alzheimer’s disease

Abstract

40 Hz sensory stimulation (“flicker”) has emerged as a new technique to potentially mitigate pathology and improve cognition in mouse models of Alzheimer’s disease (AD) pathology. However, it remains unknown how 40 Hz flicker affects neural codes essential for memory. Accordingly, we investigate the effects of 40 Hz flicker on neural representations of experience in the hippocampus of the 5XFAD mouse model of AD by recording 1,000s of neurons during a goal-directed spatial navigation task. We find that an hour of daily exposure to 40 Hz audio-visual stimulation over 8 d leads to higher coordination between hippocampal subregions CA3 and CA1 during navigation. Consistent with CA3’s role in generating sequential activity that represents future positions, 40 Hz flicker exposure increased prospective coding of future positions. In turn, prospective coding was more prominent during efficient navigation behavior. Our findings show how 40 Hz flicker enhances key hippocampal activity during behavior that is important for memory.