Fig. 5
Involvement of gal3 in the disruption of gamma oscillations in two different AD-related mouse models. a Left: Representative example traces of gamma oscillations recorded in an interface-type recording chamber in control conditions (gray) and in slices pre-incubated for 15 min with 50 nM Aβ42 (red) or 50 nM Aβ42 + 10 µM TD139 (blue). Right: Representative power spectra from network activity (0–100 Hz) in CA3 hippocampus for each condition. b Left: Representative example traces of gamma oscillations recorded in CA3 of hippocampal slices from WT (gray), 5 × FAD (red) and 5 × FAD-Gal3KO (blue) mice in a submerged-type recording chamber. Right: Representative power spectra from network activity (0–100 Hz) in CA3 hippocampus for each animal group. c Summary of gamma oscillation power (20–80 Hz) showing that TD139 counteracted Aβ42-induced decrease of gamma power (control: 10.4 ± 2.24 × 10–09 V2, n = 8, N = 4; Aβ42: 2.23 ± 0.36 × 10–09 V2, n = 8, N = 4; P = 0.0478 vs control, P = 0.0040 vs Aβ42 + TD139, Aβ42 + TD139: 13.9 ± 2.9 × 10–09 V2, n = 10, N = 3; P = 0.2809 vs control). d Summary of the Cr showing that TD139 prevented Aβ42-induced deterioration of gamma rhythmicity (control: 0.84 ± 0.01, n = 8, N = 4; Aβ42: 0.75 ± 0.02, n = 8, N = 4; P < 0.001 vs control, P < 0.0001 vs Aβ42 + TD139, Aβ42 + TD139: 0.85 ± 0.01, n = 10, N = 3; P = 0.7034 vs control). Inset: Representative example of the autocorrelation function performed on gamma oscillations recorded in the conditions mentioned in a. e Quantification of gamma oscillation power (20–80 Hz) showing that the absence of gal3 signaling in 5 × FAD mice prevented the gamma power reduction typical of this AD mouse model and resulted in gamma power similar to WT mice (WT: 1.27 ± 0.18 × 10–09 V2, n = 11, N = 4, 5 × FAD: 0.55 ± 0.03 × 10–09 V2, n = 11, N = 4, 5 × FAD-Gal3KO: 1.28 ± 0.25 × 10–09 V2, n = 10, N = 4). Note that deletion of gal3 in isolation did not affect gamma oscillation power in the Gal3KO mice: 1.34 ± 0.14 × 10–09 V2, n = 17, N = 4. Statistics performed: Kruskal–Wallis test followed by Dunn’s multiple comparisons. A summary is provided in Additional file 2: Table S3. f Summary of peak frequency revealing that 5 × FAD mice had slower gamma oscillations (WT: 28.2 ± 0.61 Hz, n = 11, N = 4, 5 × FAD: 24.6 ± 0.58 Hz, n = 11, N = 4, 5 × FAD-Gal3KO: 26.4 ± 1.05 Hz, n = 10, N = 4, Gal3KO: 26.8 ± 0.87 Hz, n = 17, N = 4). Statistics performed: ordinary one-way ANOVA followed by Holm-Sidak’s multiple comparisons test. A summary is provided in Additional file 2: Table S4. In parallel to the lower power and slower central frequency of gamma oscillation, 5 × FAD mice displayed gamma oscillations with larger frequency variance (WT: 7.43 ± 0.48 Hz, n = 11, N = 4, 5 × FAD: 10.9 ± 0.69 Hz, n = 10, N = 4, 5 × FAD-Gal3KO: 7.55 ± 0.64 Hz, n = 10, N = 4, Gal3KO: 8.52 ± 0.62 Hz, n = 17, N = 4). Statistics performed: Kruskal–Wallis test followed by Dunn’s multiple comparisons. A summary is provided in Additional file 2: Table S5 and Additional file 1: Fig. S9. g Left panels, from top to bottom: Aβ (in grey) plaque size was reduced in CA3 area of the 5 × FAD-Gal3KO mouse hippocampus. Microglia (Iba1 in green) surrounding the plaques in both 5 × FAD and 5 × FAD-Gal3KO. Labelling corresponding to the specific antibody against Gal3 (in red) was abolished in 5 × FAD-Gal3KO mouse hippocampus. Right panels: merge of the labeling on the left panels. Scale bar 500 μm. DG: Dentate gyrus. h Quantification of the mean area of Aβ plaque labelling in CA3 area of 6-month-old mice in both 5 × FAD (864 ± 135.7 μm2, n = 21, N = 3) and 5 × FAD-Gal3KO (328.9 ± 112.7 μm2, n = 7, N = 3). P = 0.0225, two-tailed Mann Whitney test. n: number of plaques; N: number of mice per group. Data are presented as mean ± SE. Significance levels are shown as *P < 0.05, **P < 0.01, ***P < 0.001. n.s.: no significant statistical difference. In panels c–f, n: number of slices, N: number of animals