Figure 2. RyR2-E4872Q^+/− Prevents Neuronal Hyperactivity of 5xFAD^+/− Hippocampal CA1 Neurons In Vivo.

(A–D) Two-photon Ca²⁺ images of the hippocampal CA1 region of 5- to 6-month-old WT (A), 5xFAD^+/− (B), 5xFAD^+/−/EQ^+/− (C), and EQ^+/− (D) mice in vivo. Colored dots indicate the number of Ca²⁺ transients per minute.

(E–H) Ca²⁺ traces of the five neurons circled in (A)–(D), respectively.

(I–L) Histograms showing the frequency distribution of Ca²⁺ transients in (I) WT (8 mice, 2,375 cells), (J) 5xFAD^+/− (8 mice, 1,708 cells), (K) 5xFAD^+/−/EQ^+/− (8 mice, 2,283 cells), and (L) EQ^+/− (8 mice, 2,392 cells). Pie charts show the relative proportions of silent, normal, and hyperactive neurons as defined previously (Busche, 2018; Busche et al., 2008, 2012).

(M) Cumulative probability functions showing frequency distributions of spontaneous Ca²⁺ transients in the CA1 region of WT (black), 5xFAD^+/− (red), 5xFAD^+/−/EQ^+/− (green), and EQ^+/− (blue) mice (Kruskal-Wallis test with Dunn’s multiple comparisons test).

(N) Mean Ca²⁺ transient frequency in the WT, 5xFAD^+/−, 5xFAD^+/−/EQ^+/−, and EQ^+/− CA1 region.

(O–Q) Percentage of silent (O), normal (P), and hyperactive (Q) cells in the WT, 5xFAD^+/−, 5xFAD^+/−/EQ^+/−, and EQ^+/− CA1 region.

Scale bars: 10 μm. Data shown are the median and range (Kruskal-Wallis test with Dunn-Bonferroni post hoc test; *p < 0.5, **p < 0.01 versus WT, #p < 0.05, ##p < 0.01; 5xFAD^+/−/EQ^+/− versus 5xFAD^+/−). See also Figures S2 and S3.