Fig. 4: Selective APOE4 removal from neurons rescues morpho-electric and excitability phenotypes of CA3 PCs in young fE4-KI/Syn-Cre+ mice.
a, Representative traces of CA3 PC membrane potential (top) response to a 150-pA, 1-second depolarizing current injection (bottom) in E3-KI, fE4-KI/Syn1-Cre+ and fE4-KI/Syn1-Cre− mice. Compared to their Cre− littermates that express APOE4 in neurons, young fE4-KI/Syn1-Cre+ mice display full normalization of all morpho-electric and excitability parameters to E3-KI levels: b, input current–firing rate (I–F) curves; c, output gain values; d, rheobase values; e, spike latency values; f, Cm values; g, Rin values. h–j, Neurons in fE4-KISyn1-Cre+ mice show abolished Cm–IE correlations, whereas neurons in Cre− mice retain these correlations across Cm versus output gain (h), Cm versus rheobase (i) and Cm versus spike latency (j). All data are represented as mean ± s.e.m. All panels: E3-KI: eight mice, n = 19 cells; fE4-KI/Syn1-Cre+: three mice, n = 19 cells; fE4-KI/Syn1-Cre−: three mice, n = 19 cells. Significance was assessed using one-way ANOVA with post hoc Tukey’s multiple comparisons test.
