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. 2019 Nov 29;8:e50333. doi: 10.7554/eLife.50333

Figure 1. AD neurons show enhanced excitability compared to isogenic control neurons.

(A) Spontaneous action potentials (sAP) at resting membrane potential (RMP). WT/WT hiPSC-derived cerebrocortical neuron data in black, M146V/WT and APPswe/WT in red. (B) Quantification of sAP frequency. (C) Evoked APs in neurons hyperpolarized to −60 mV. Single traces (insets). (D–H) Neuronal membrane and AP properties. Quantification of resting membrane potential (RMP, (D), AP threshold (APthreshold, (E); AP height (F); width at AP half height (G); AP decay slope (H). (I). Quantification of cell capacitance (Cm), reflecting neuronal size. Data are mean ± SEM. Statistical significance analyzed by ANOVA with post hoc Dunnett’s test. Exact p values for comparison to WT are listed in the bar graphs in this and subsequent figures. Unless otherwise stated, total number of neurons quantified is listed above the bars in this and subsequent electrophysiology figures.

Figure 1—source data 1. Excel files containing data shown as summary bar graph in Figure 1B,D–I.

Figure 1.

Figure 1—figure supplement 1. AD hiPSC-derived neuronal cultures express cortical neuronal markers and aberrant Aβ levels compared to isogenic controls.

Figure 1—figure supplement 1.

(A) DNA sequencing to confirm the presence of mutations in hiPSC-derived neural progenitor cells with WT/WT, M146V/WT, and APPswe/WT genotypes. (B) hiPSC-derived neurons showing FOXG1 and Tuj1 expression. (C) hiPSC-derived neurons showing FOXG1 and CTIP2 expression. (D) Ratio of Aβ42/Aβ40 quantified by ELISA from cultures at 5 weeks. (E) Quantification of Aβ levels normalized to total protein from lysates at 5 weeks. Data are mean ± SEM. Statistical significance analyzed by ANOVA with post hoc Dunnett’s test for multiple comparisons. Number of independent experiments listed above the bars.
Figure 1—figure supplement 2. ΔE9/WT neurons show enhanced excitability compared to isogenic control neurons.

Figure 1—figure supplement 2.

(A) Spontaneous action potentials (sAP) at resting membrane potential (RMP). WT/WT hiPSC-derived cerebrocortical neuron data in black, ΔE9/WT in red. (B) Quantification of sAP frequency. (C) Evoked APs in neurons hyperpolarized to −60 mV. Single traces (insets). (D–H) Neuronal membrane and AP properties. Quantification of resting membrane potential (RMP, (D), AP threshold (APthreshold, (E); AP height (F); width at AP half height (G); AP decay slope (H). (I) Quantification of cell capacitance (Cm), reflecting overall neuronal size. Data are mean ± SEM. Statistical significance analyzed by two-tailed unpaired Student’s t-test.