Fig. 1: APOE4 induces early region-specific hippocampal network hyperexcitability that predicts future learning impairment.
a, Example raw LFP trace of an IIS from CA3 PC layer. b, CA3 IIS rates in two independent cohorts of young (5–10 months) and aged (12–18 months) E3-KI and E4-KI mice. c, IIS rates in the DG of young and aged E3-KI and E4-KI mice. d, IIS rates in CA1 of young and aged E3-KI and E4-KI mice. e, Timeline of experiments for the longitudinal cohort shown in f–j. f, Average daily escape latency on MWM for the longitudinal E3-KI and E4-KI cohort at 6–8 months of age. g, Average daily escape latency on MWM for the longitudinal E3-KI and E4-KI cohort at 14–18 months of age. h, CA3 IIS rate at 5–10 months predicts escape latency on hidden platform day 2 trial at 14–18 months in E4-KI mice but not in E3-KI mice. Pearson’s correlation analysis (two-sided). i, DG IIS rate at 5–10 months predicts escape latency on hidden platform day 2 trial at 14–18 months in E4-KI mice but not in E3-KI mice. j, CA1 IIS rate at 5–10 months does not predict escape latency on hidden platform day 2 trial at 14–18 months in E-KI mice of either genotype. All data are represented as mean ± s.e.m. Significance was assessed using unpaired two-tailed t-test or Mann–Whitney U-test. For IIS rates (b–d): n = 13 and 17 for young E3-KI and E4-KI mice (16 E4-KI mice for DG IIS); n = 13 and 16 for aged E3-KI and E4-KI mice. For MWM tests (f,g): n = 13 each for young E3-KI and E4-KI mice; n = 13 and 15 for aged E3-KI and E4-KI mice. For h–j: n = 9 and 11 for E3-KI and E4-KI mice, respectively. mo, months. Icons in e created in BioRender; Zilberter, M. https://BioRender.com/tyaw8fo (2025).
