Figure 1: Astrocytes are hyperactive in APPPS1 mice.

(a,b) Cells were labelled with the green-fluorescent calcium indicator OGB-1 AM and astrocytes were identified by co-labelling with red-fluorescent SR101 (arrows indicate astrocytes identified by double labelling; the open arrowhead illustrates a neuron labelled with OGB-1). Plaques were labelled with the blue-fluorescent plaque marker methoxy-XO4 (arrowheads). In astrocytes positive for both OGB-1 and SR101 (labelled 1–17 in a), spontaneous calcium activity could be detected (arrowheads), ranging from inactive to hyperactive. Inactivity, activity (green traces in b) and hyperactivity (red traces in b) were defined as 0, 0.1–0.4 and >0.4 events per min, respectively. Scale bar, 50 μm. (c,d) Frequency histograms revealed that significantly more astrocytes are hyperactive and less astrocytes are inactive in APPPS1 mice compared with age-matched wild-type littermates (33.8% versus 4.1%; P<0.05, χ²-test; based on 5-min time lapse series from n=206 astrocytes from n=9 APPPS1 mice versus n=299 astrocytes from n=10 wild-type mice and 20-min time-lapse series from n=69 astrocytes from n=4 APPPS1 mice versus n=67 astrocytes from n=3 wild-type mice, respectively).