Hippocampal astrocytes are hyperactive in APPPS1 mice. (A) AAV-GfaABC1D-cytoGCaMP6f was injected into the dorsal hippocampus in APPPS1 mice or WT littermates, and a window above the right dorsal hippocampus (HC) was created for imaging. Mice were imaged 4 wk later. (B) Hippocampal astrocytes labeled with cytoGCaMP6f in vivo (arrows). Aβ plaques were labeled with methoxy-X04 (arrowheads). Blood vessels were labeled with Texas Red dextran. Bar, 50 µm. (C) Spontaneous calcium events in hippocampal astrocytes labeled with cytoGCaMP6f in vivo. Traces correspond to astrocytes displayed in Video 1. (D–F) Spontaneous calcium amplitudes of hippocampal astrocytes were higher in APPPS1 mice compared with WT littermates (*, P < 0.05, Mann–Whitney test; mean ± SEM), whereas the full duration at half maximum (FDHM) was similar. The fraction of active astrocytes was higher in APPPS1 mice (**, P < 0.001, Fisher’s exact test; APPPS1, n = 149 cells from four mice, age, 11 mo; WT, n = 244 cells from six age-matched mice).