Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory deficits. Abnormal accumulation of β-amyloid in AD disrupts neural circuits involved in memory processing. GABAergic interneurons are crucial for memory encoding and retrieval, but how β-amyloid affects their function in AD is not well understood. We used in vivo Ca2+ imaging to study parvalbumin-expressing (PV) interneurons in the retrosplenial cortex (RSC), a region affected early in AD.

We found that the number of PV interneurons that encode memory is significantly decreased in the mouse model of AD (5XFAD mice) compared to healthy mice. Also, while the activity of these memory-encoding PV interneurons selectively increased during memory retrieval in healthy  mice, such dynamic change was absent in the 5XFAD mice. Additionally, silencing PV interneurons in healthy mice using optogenetics led to memory deficits similar to those observed in 5XFAD mice, while activating PV interneurons in the AD mice fully restored memory retrieval.

These findings demonstrate that PV interneuron dysfunction in AD disrupts memory processes and suggest PV interneurons as a potential therapeutic target for AD.