Fig. 1
Dorsal CA1 PNs are hyperexcitable in hAPP-J20 mice. (A) Images of brain slices showing the region of dorsal hippocampus (scale bar, 500 μm), a representative PV neuron and a representative pyramidal neuron (PN) (scale bars, 50 μm) for recordings. (B) The numbers of spikes generated in dCA1 PNs of WT and hAPP-J20 mice (2.5 months) in response to depolarizing current injections (WT, n = 29 cells from 10 mice; J20, n = 28 cells from 9 mice). Two-way ANOVA: genotype (hAPP), F (1, 55) = 6.503, p = 0.0136; current step, F (10, 550) = 557.3, p < 0.0001; interaction, F (10, 550) = 2.630, p = 0.0039; *p < 0.05, **p < 0.01 with Bonferroni’s post-hoc test. (C) The numbers of spikes generated in dCA1 PNs of WT and hAPP-J20 mice (6 months) in response to depolarizing current injections (WT, n = 32 cells from 12 mice; J20, n = 31 cells from 11 mice). Two-way ANOVA: genotype (hAPP), F (1, 61) = 15.69, p = 0.0002; current step, F (2.408, 146.9) = 585.8, p < 0.0001; interaction, F (10, 610) = 5.962, p < 0.0001; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 with Bonferroni’s post-hoc test. (D) The numbers of spikes generated in vCA1 PNs of WT and hAPP-J20 mice (6 months) in response to depolarizing current injections (WT, n = 27 cells from 9 mice; J20, n = 28 cells from 10 mice). Two-way ANOVA with Bonferroni’s post-hoc test: genotype (hAPP), F (1,53) = 0.4698, p = 0.4961; current step, F (2.426,128.6) = 411.6, p < 0.0001; interaction, F (10,530) = 0.5348, p = 0.8658. (E) The numbers of spikes generated in dCA1 PV neurons of WT and hAPP-J20 mice (6 months) in response to depolarizing current injections (WT, n = 23 cells from 9 mice; J20, n = 25 cells from 10 mice). Two-way ANOVA with Bonferroni’s post-hoc test: genotype (hAPP), F (1, 46) = 0.1271, p = 0.7231; current step, F (1.944, 89.41) = 630.8, p < 0.0001; interaction, F (10, 460) = 1.135, p = 0.3342. (F) Representative traces of the initial firing frequency in the dCA1 PNs of WT and hAPP-J20 mice (6 months). (G) Quantification of the initial frequency in the dCA1 PNs (WT, n = 32 cells from 10 mice; J20, n = 31 cells from 10 mice). Unpaired t-test: t (61) = 3.392, p = 0.0012. **p < 0.01. (H) Representative traces of the input resistance in the dCA1 PNs of WT and hAPP-J20 mice (6 months). (I) Quantification of the input resistance in the dCA1 PNs (WT, n = 32 cells from 10 mice; J20, n = 31 cells from 10 mice). Unpaired t-test: t (61) = 2.946, p = 0.0046. **p < 0.01. (J) The rheobase of dCA1 PNs in 6-month-old WT and hAPP-J20 mice (WT, n = 32 cells from 10 mice; J20, n = 31 cells from 10 mice). Unpaired t-test: t (61) = 3.572, p = 0.0007. ***p < 0.001. (K) The resting membrane potential (RMP) of dCA1 PNs in 6-month-old WT and hAPP-J20 mice (WT, n = 32 cells from 10 mice; J20, n = 31 cells from 10 mice). Unpaired t-test: t (61) = 0.4743, p = 0.6370. (L) The threshold for generation of action potentials of dCA1 PNs in 6-month-old WT and hAPP-J20 mice (WT, n = 32 cells from 10 mice; J20, n = 31 cells from 10 mice). Unpaired t-test: t (61) = 0.9104, p = 0.3662. (M) Representative traces of the spontaneous action potential (sAP) of dCA1 PNs in WT and hAPP-J20 mice (6 months). (N) Quantification of sAP in the dCA1 PNs (WT, n = 26 cells from 10 mice; J20, n = 26 cells from 10 mice). Unpaired t-test: t (50) = 2.563, p = 0.0134