Fig. 5: Impact of amyloid plaque proximity on the dynamics of neuronal activity.
From: Long-term dynamics of aberrant neuronal activity in awake Alzheimer’s disease transgenic mice
a Representative FOV (dashed rectangle) within a plane of a z-stack (shown is the mRuby2 channel in grey scale), used to measure the distances between plaques and neurons; GCaMP6s (green), mRuby2 (red), plaques (location of plaques is derived from the methoxy-XO4 channel and indicated by dashed lines). Selected ROIs are identical in a, b. The arrow indicates the viewing angle in b. b 3D reconstruction of the imaged area shown in a; plaques (blue) and the ROIs (green). Lines connecting ROIs and plaques represent the shortest distance between a neuron and the closest plaque border. c Relative proportions of highly, intermediately and rarely active neurons and their fractional change over time in APPPS1 mice for close (<=40 µm) and distant (>40 µm from plaque border) neurons. Relative proportions of activity categories did not differ and were stable over time (fraction highly active neurons: effect of group: F1,56 = 0.44, p = 0.51, effect of time: F2,56 = 0.13, p = 0.88, group-by-time interaction effect: F2,56 = 0.78, p = 0.46, fraction of intermediately active neurons: effect of group: F1,56 = 0.18, p = 0.68, effect of time: F2,56 = 0.5, p = 0.61, group-by-time interaction effect: F2,56 = 1.14, p = 0.33, fraction rarely active neurons: effect of group: F1,56 = 0.68, p = 0.41, effect of time: F2,56 = 2.62, p = 0.08, group-by-time interaction effect: F2,56 = 1.16, p = 0.32; two-way repeated measures ANOVA, close n = 15, distant n = 15 experiments (containing 326 neurons close, 326 neurons distant)). d Fraction of neurons in each activity category that remain within the same category over the whole imaging period (close (gray) and distant (white) neurons, highly active neurons p < 10−4, intermediately active neurons p = 0.005, rarely active neurons p < 10−3, neurons pooled, data are median ± 95% CI). e Activity change distribution for neurons within different plaque-distance bins. The majority of neurons (>75%) changed their activity within a range of ±2 transients/min (gray area) (week 0–2: F3,615 = 0.47, p = 0.7, one way ANOVA; week 0–4: F3,615 = 0.97, p = 0.41, one way ANOVA, neurons pooled). **P < 0.01, ***P < 0.001.
