TY - JOUR TI - Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice AU - Åbjørsbråten, Knut Sindre AU - Skaaraas, Gry HE Syverstad AU - Cunen, Céline AU - Bjørnstad, Daniel M AU - Binder, Kristin M Gullestad AU - Bojarskaite, Laura AU - Jensen, Vidar AU - Nilsson, Lars NG AU - Rao, Shreyas B AU - Tang, Wannan AU - Hermansen, Gudmund Horn AU - Nagelhus, Erlend A AU - Ottersen, Ole Petter AU - Torp, Reidun AU - Enger, Rune A2 - Nelson, Mark T A2 - Aldrich, Richard W A2 - Nelson, Mark T A2 - Stobart, Jillian L VL - 11 PY - 2022 DA - 2022/07/14 SP - e75055 C1 - eLife 2022;11:e75055 DO - 10.7554/eLife.75055 UR - https://doi.org/10.7554/eLife.75055 AB - Increased astrocytic Ca2+ signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca2+ 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 Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRABNE, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca2+ responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca2+ activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease. KW - Alzheimer's disease KW - calcium imaging KW - norepinephrine KW - astrocytes JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -