Fig. 3
Disrupted functions of HCNs in dCA1 PNs of hAPP-J20 mice or in dCA1 PNs of WT mice treated with oligomeric Aβ. (A) Representative traces elicited by a series of negative current injections of dCA1 PNs in WT and hAPP-J20 mice. (B) The sag ratio at the − 200 pA current injection detected from the dCA1 PNs of hAPP-J20 and WT mice. Unpaired t-test: t (61) = 2.395, p = 0.0197. (C) Sag amplitudes of dCA1 PNs at − 200 to 0-pA current injections. Two-way ANOVA: genotype (hAPP), F (1, 61) = 31.81, p < 0.0001; current step, F (1.225, 74.71) = 450.0, p < 0.0001; interaction, F (4, 244) = 16.29, p < 0.0001; **p < 0.01, ****p < 0.0001 with Bonferroni’s post-hoc test. (D) Representative traces of the HCN-conducted Ih currents in dCA1 PNs of WT and hAPP-J20 mice. (E) The HCN-conducted Ih currents in dCA1 PNs of hAPP-J20 and WT mice (WT, n = 10 cells from 5 mice; J20, n = 10 cells from 5 mice). Two-way ANOVA: genotype (hAPP), F (1, 18) = 18.04, p = 0.0005; voltage step, F (6, 108) = 124.7, p < 0.0001; interaction, F (6, 108) = 8.998, p < 0.0001; **p < 0.01, ****p < 0.0001 with Bonferroni’s post-hoc test. (F) Representative traces elicited by a series of negative current injections of dCA1 PVs in WT and hAPP-J20 mice. (G) The sag ratio at the − 200 pA current injection detected from the dCA1 PVs of hAPP-J20 and WT mice. Unpaired t-test: t (46) = 1.812, p = 0.0765. (H) The sag amplitudes of PVs from hAPP-J20 and WT mice. Two-way ANOVA: genotype (hAPP), F (1, 46) = 2.134, p = 0.1508; current step, F (1.025, 47.16) = 243.4, p < 0.0001; interaction, F (4, 184) = 0.7310, p = 0.5719. (I) Representative traces of the HCN-conducted Ih currents in dCA1 PVs of WT and hAPP-J20 mice. (J) The HCN-conducted Ih currents of dCA1 PVs of hAPP-J20 and WT mice (WT, n = 23 cells from 9 mice; J20, n = 25 cells from 10 mice). Two-way ANOVA: genotype (hAPP), F (1, 23) = 0.005643, p = 0.9408; voltage step, F (2.001, 46.03) = 224.3, p < 0.0001; interaction, F (6, 138) = 0.3319, p = 0.9192. (K) Representative bands showing the Aβ oligomers by western blotting with 6E10. (L) Representative traces of the HCN-conducted Ih currents in dCA1 PNs of WT mice sampled from baseline, Aβ oligomers (10 nM) and Aβ + cAMP treatment, respectively. (M) Quantification of the Ih currents in dCA1 PNs from the three groups in (L) (baseline, n = 15 cells from 5 mice; Aβ, n = 15 cells from 5 mice; Aβ + cAMP, n = 14 cells from 5 mice). Two-way ANOVA with Bonferroni’s post-hoc test: drug, F (2, 41) = 5.383, p = 0.0084; voltage step, F (6, 246) = 506.2, p < 0.0001; interaction, F (12, 246) = 3.875, p < 0.0001