Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice
Knut Sindre Åbjørsbråten,
Gry HE Syverstad Skaaraas,
Céline Cunen,
Daniel M Bjørnstad,
Kristin M Gullestad Binder,
Laura Bojarskaite,
Vidar Jensen,
Lars NG Nilsson,
Shreyas B Rao,
Wannan Tang,
Gudmund Horn Hermansen,
Erlend A Nagelhus,
Ole Petter Ottersen,
Reidun Torp,
Rune Enger
Affiliations
Knut Sindre Åbjørsbråten
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Gry HE Syverstad Skaaraas
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Céline Cunen
Statistics and Data Science group, Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Norwegian Computing Center, Oslo, Norway
Daniel M Bjørnstad
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Kristin M Gullestad Binder
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Laura Bojarskaite
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway
Vidar Jensen
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Lars NG Nilsson
Department of Pharmacology, University of Oslo and Oslo University Hospital, Oslo, Norway
Shreyas B Rao
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Wannan Tang
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Gudmund Horn Hermansen
Statistics and Data Science group, Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
Erlend A Nagelhus
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Ole Petter Ottersen
Office of the President, Karolinska Institutet, Stockholm, Sweden
Reidun Torp
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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.
