Astrocyte-neuronal network interplay is disrupted in Alzheimer's disease mice.

Abstract

Alzheimer's disease (AD) is associated with senile plaques of beta-amyloid (Aβ) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aβ on astroglial and neuronal network function remains unknown. Simultaneously monitoring astrocyte calcium and electric neuronal activities, we quantified the impact of Aβ on sensory-evoked cortical activity in a mouse model of AD. At rest, cortical astrocytes displayed spontaneous hyperactivity that was related to Aβ density. Sensory-evoked astrocyte responsiveness was diminished in AD mice, depending on the density and distance of Aβ, and the responses showed altered calcium dynamics. Hence, astrocytes were spontaneously hyperactive but hypo-responsive to sensory stimulation. Finally, AD mice showed sensory-evoked electrical cortical hyperresponsiveness associated with altered astrocyte-neuronal network interplay. Our findings suggest dysfunction of astrocyte networks in AD mice may dysregulate cortical electrical activity and contribute to cognitive decline.