Impaired astrocytic Ca ²⁺ signalling in awake Alzheimer’s disease transgenic mice

Increased astrocytic Ca ²⁺ signaling related to amyloid plaques has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca ²⁺ signalling in such mice without the confounding effects of anesthesia. Here, we employ an event-based algorithm to assess astrocytic Ca ²⁺ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca ²⁺ response to locomotion and an uncoupling of pupil responses and astrocytic Ca ²⁺ signalling in 15-months old plaque-bearing mice. This points to a potential decoupling of neuromodulatory activation and astrocytic Ca ²⁺ activity, which may account for some of the cognitive dysfunctions observed in Alzheimer’s disease.