Abstract Neurodegeneration-related decline affects the health of millions of patients with Alzheimer's disease worldwide and imposes a heavy emotional and financial burden on patients, their families, and their communities. Commonly-used brain activity recording methods cannot probe single-cell activity and therapeutic approaches are evaluated based on their success at relieving disease symptoms, and not their ability to restore normal neuronal functionality. Therefore, the relationships between age-related neurodegeneration, impaired brain circuitry, and disrupted neuronal activity patterns in Alzheimer's disease are poorly understood, and there are clear knowledge gaps regarding how they change during disease progression. Drs. Dana, Raber and their colleagues offer a new approach for chronic recording of the activity from tens of thousands of neurons across the mouse cortex, with single-cell resolution, and in freely- moving mice. This approach will be used for longitudinal recording of cortex-wide activity in mouse model of Alzheimer's disease-like degeneration during cognitive and behavioral tasks, in order to identify neurodegeneration-related changes in cortical activity patterns.