Article Figures & Data
Figures
- Figure 1.
Normal OFT performance and body weight in AppNL-G-F/wt and AppNL-G-F/NL-G-F mice. A, B, Time spent in the central zone (A) and total distance traveled (B) by four- and nine-month-old mice. Bar graphs represent mean ± SEM. Each point represents an individual mouse. C, The body weight of the younger mice was measured at five and six months while the body weight of the older mice was measured at seven, nine, and 12 months. Each point represents the mean ± SEM. Detailed results of the statistical tests are described in Extended Data Figure 1-1.
- Figure 2.
AppNL-G-F/NL-G-F mice exhibit age-dependent impairments in sleep architecture. A, B, Diurnal sleep-wake cycles of six-month-old (A) and 12-month-old (B) mice. Each point represents the mean ± SEM; #p < 0.05, ###p < 0.001, mixed ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, post hoc Games–Howell multiple comparison test. C–E, Total amount of wake, NREMS, REMS, and ratio of REMS to total sleep [24 h (C), light period (D), and dark period (E)]. F, G, Number of episodes (F) and mean episode duration (G) in each stage of wake, NREMS, and REMS. H, REMS latency. Bar graphs represent the mean ± SEM. Each point represents an individual mouse; *p < 0.05, **p < 0.01, ***p < 0.001, Games–Howell multiple comparison test. Detailed results of the statistical tests are described in Extended Data Figure 2-1.
- Figure 3.
AppNL-G-F/NL-G-F mice exhibit age-dependent alterations in brain oscillatory activities. A, B, EEG power spectrum of wakefulness, NREMS, and REMS in six-month-old (A) and 12-month-old (B) mice. C–K, Comparison of δ (1–4 Hz) power (C–E), θ (7–10 Hz) power (F–H), and γ (25–45 Hz) power (I–K) during wake (C, F, I), NREMS (D, G, J), and REMS (E, H, K). L–N, Ratio of γ to δ power during wake (L), NREMS (M), and REMS (N). O, Ratio of θ to δ power during REMS. Bar graphs represent mean ± SEM. Each point represents an individual mouse; *p < 0.05, **p < 0.01, ***p < 0.001, Games–Howell multiple comparison test. Detailed results of the statistical tests are described in Extended Data Figure 3-1.
- Figure 4.
AppNL-G-F/NL-G-F mice exhibit reduced REMS following exposure to novel objects. A, Total amount of wake, NREMS, REMS, and ratio of REMS to total sleep following presentation of novel objects. B, C, Latency to sleep (B) or REMS (C) following presentation of novel objects; *p < 0.05, Games–Howell multiple comparison test. Bar graphs represent mean ± SEM. Each point represents an individual mouse. Detailed results of the statistical tests are described in Extended Data Figure 4-1.
- Figure 5.
Impaired performance of AppNL-G-F/NL-G-F mice in trace FC. A, Movement of each seven-month-old and 13-month-old mouse before and during the first US; ###p < 0.001, mixed ANOVA. B, Percent time spent freezing during habituation or CS on day 1 (training). Each point represents mean ± SEM; ##p < 0.01, ###p < 0.001, mixed ANOVA; *p < 0.05, **p < 0.01, post hoc Games–Howell multiple comparison test. C, Percent time spent freezing during CS on day 2 (retrieval). Bar graphs represent the mean ± SEM. Each point represents an individual mouse; *p < 0.05, Games–Howell multiple comparison test. Detailed results of the statistical tests are described in Extended Data Figure 5-1.
- Figure 6.
Correlations between the amount of time spent in each sleep stage and the performance in trace FC. A–L, Correlation between the total amount of REMS or NREMS and the percent time spent freezing either during the third CS on day 1 (training) or during CS on day 2 (retrieval) in WT, AppNL-G-F/wt and AppNL-G-F/NL-G-F mice of the younger age. M–X, Correlation between the total amount of REMS or NREMS and the percent time spent freezing either during the third CS on day 1 (training) or during CS on day 2 (retrieval) in WT, AppNL-G-F/wt and AppNL-G-F/NL-G-F mice of the older age. Each point represents an individual mouse. The line in each graph represents the regression line. Pearson’s correlation coefficient (r) and p value are provided.
- Figure 7.
Aβ deposition in brain areas related to REMS regulation in AppNL-G-F/wt and AppNL-G-F/NL-G-F mice. A–H, Representative images of brain sections immunostained for Aβ. Images in B, D, F, H are higher magnifications of the areas enclosed in A, C, E, G. Sections contain the following brain regions: MSDB (A, B), hippocampus and cortex (C, D), pontine tegmental area (E, F), and ventral medulla (G, H). Scale bar: 2.5 mm (A, C, E, G) and 1.0 mm (B, D, F, H). I–M, Quantification of Aβ plaque areas in MSDB (I), hippocampus (J), cortex (K), pontine tegmental area (L), and ventral medulla (M). Bar graphs represent the mean ± SEM. Each point represents an individual mouse; *p < 0.05, **p < 0.01, Welch’s t test. Detailed results of the statistical tests are described in Extended Data Figure 7-1.
Extended Data
Extended Data Figure 1-1
Detailed results of the statistical analyses in Figure 1. Download Figure 1-1, XLSX file.
Extended Data Figure 2-1
Detailed results of the statistical analyses in Figure 2. Download Figure 2-1, XLSX file.
Extended Data Figure 3-1
Detailed results of the statistical analyses in Figure 3. Download Figure 3-1, XLSX file.
Extended Data Figure 4-1
Detailed results of the statistical analyses in Figure 4. Download Figure 4-1, XLSX file.
Extended Data Figure 5-1
Detailed results of the statistical analyses in Figure 5. Download Figure 5-1, XLSX file.
Extended Data Figure 7-1
Detailed results of the statistical analyses in Figure 7. Download Figure 7-1, XLSX file.
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