Figure 1.

Functional impairments of cortical neurons in mouse models of AD in vivo. (a) In vivo two-photon calcium image of layer 2/3 neurons in the frontal cortex of a wild-type (WT) mouse (top panel) and an APP23 × PS45 transgenic mouse with thioflavin-S labelled amyloid plaques (bottom panel). (b) Spontaneous Ca²⁺-transients from neurons marked in (a): blue, silent neurons; black, normal neurons; red, hyperactive neurons. (c) Relative fractions of silent (blue), normal (green) and hyperactive (red) neurons. (d) Activity map of cortical region in an APP23 × PS45 mouse with neurons colour-coded according to the frequency of their spontaneous Ca²⁺ transients. Broken line circles are centred at the respective plaques and delineate the area located less than 60 µm from the plaque border. Adapted from [18]. Reproduced with permission from AAAS. (e) Bar graphs showing the abundance of silent (blue), normal (green) and hyperactive (red) neurons at different distances from the border of the nearest plaque. (f) Age-dependent increase in plaque burden in the cortex of APP23 × PS45 mice. (g,h) Relative proportions of silent (g) and hyperactive (h) neurons in WT (black) and APP23 × PS45 (red) mice at four different age groups (1.5–2, 3–3.25, 4–4.5 and 8–10 months). Error bars indicate s.e.m. Adapted from [19].