Fig. 3.
The inhibitory synaptic response of the CA1 pyramidal neuron was attenuated in the 5XFAD mouse model. A Representative traces showing miniature IPSCs (mIPSCs) in the CA1 pyramidal neuron of WT and 5XFAD mice. B, C Amplitudes (B) and frequency (C) of mIPSCs, n(WT) = 25 neurons/11 mice, n(FAD) = 23 neurons/8 mice, were subjected to unpaired Student’s t-test, *p = 0.0192 for amplitude, *p = 0.014 for frequency. D, E Cumulative distribution plots for amplitude (D) and frequency (E) of mIPSCs in WT and 5XFAD mice. F Input–output (I-O) relationship between evoked IPSCs (eIPSCs) and incremental stimulation intensities (in μA) 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 (WT, 21.52 ± 3.25, 63.56 ± 13.96, 182.98 ± 47.65, 265.61 ± 49.33, 298.14 ± 52.68, 352.74 ± 50.99, 412.40 ± 45.03, 548.96 ± 43.79, 662.15 ± 41.27, 764.10 ± 25.28 pA, respectively, n = 14 neurons/4 mice; FAD, 14.50 ± 4.44, 64.64 ± 26.56, 131.58 ± 39.08, 204.07 ± 37.37, 267.47 ± 37.74, 296.47 ± 34.27, 355.09 ± 34.99, 353.79 ± 34.24, 386.77 ± 37.57, 412.59 ± 37.39 pA, respectively, n = 17 neurons/7 mice; with two-way ANOVA analysis followed by Bonferroni’s multiple comparisons test, *p < 0.05 under 80 μA stimulus intensity, ***p < 0.001 under 90 μA stimulus intensity, ****p < 0.0001 under 100 μA stimulus intensity), and the insets show representative traces of WT and FAD slices. G Input/output slope of each cell was analyzed with unpaired Student’s t-test, ****p < 0.0001. H Representative traces (insets) and plot showing the paired-pulse ratio (P2/P1, PPR) at interstimulus intervals of 50, 100, and 200 ms (WT, 1.32 ± 0.05, 1.05 ± 0.03, 0.93 ± 0.03, respectively, n = 15 neurons/4 mice; FAD, 2.32 ± 0.26, 1.84 ± 0.14, 1.45 ± 0.23, 1.14 ± 0.06, respectively, n = 16 neurons/6 mice, with unpaired Student’s t-test, and Welch’s correction was applied in 50 ms interval, p = 0.0008, 0.11, 0.0044, respectively). I GABAA receptor subunit α1 was immunostained (green) in WT and 5XFAD brain sections, and regions of interest (ROI) in the hippocampus were separated by a dashed line. MAP2 immunostaining (red) was used as internal control, and the cell nucleus was labeled by Hoechst (blue). The bar scale is 500 μm. J Mean gray value of α1-positive intensity (divided by ROI area) measured with the ImageJ software was subjected to unpaired Student’s t-test for each subregion of the hippocampus, *p < 0.05 vs. WT, n = 4 mice per group