ΔFosB Decreases Excitability of Dorsal Hippocampal CA1 Neurons

ΔFosB enhances spike frequency adaptation. A, Representative spikes at maximal depolarizing current injection in dHPC CA1 neurons transduced by HSV-GFP (GFP), HSV-GFP + ΔFosB (ΔFosB), and HSV-GFP + ΔJunD (ΔJunD). B, The maximal depolarizing current was used to assess spike frequency adaptation among GFP (n = 21 cells; n = 8 mice), ΔFosB (n = 19 cells; n = 9 mice), and ΔJunD (n = 14 cells; n = 5 mice). No differences were observed in maximal current; p > 0.05 (one-way ANOVA). C, Mean ISI (in ms) at the maximal step across groups. Mean ISI was increased by ΔFosB; *p < 0.05 compared with GFP (one-way ANOVA; Holm–Sidak comparisons). D, Number of APs at the maximal step across groups. ΔFosB significantly decreased the number APs; *p < 0.05 compared with GFP (one-way ANOVA; Holm–Sidak comparisons). E, Latency from the onset of the maximal step and the first spike was assessed for each group. ΔFosB increased the latency compared with GFP; *p < 0.05 (one-way ANOVA; Holm–Sidak comparisons). F, ISI for the first and last pair of spikes at the maximal step for each group. ISI at the last pair of spikes was increased by ΔFosB compared with GFP; **p < 0.01 (two-way repeated-measures ANOVA; Holm–Sidak comparisons). All graphs display means ± SEM.

ΔFosB decreases I_h. A–C, Representative voltage trace to a hyperpolarizing current step showing I_h in hippocampal CA1 neurons expressing GFP (n = 21 cellls; n = 8 mice), ΔFosB (n = 19 cells; n = 9 mice), and ΔJunD (n = 13 cells; n = 5 mice), respectively. Arrows indicate amplitude measured at peak and S.S. D−F, I–V curves from hyperpolarizing current injections (0 to −500 pA) at peak and S.S. in GFP, ΔFosB, and ΔJunD cells. GFP cells had significant differences between peak and S.S. across currents (from −500 to −200 pA), indicative of I_h. ***p < 0.001 (two-way ANOVA; Holm–Sidak comparisons). Differences between peak and S.S. were comparably reduced in both ΔFosB (only different at steps −400 and −300 pA) and ΔJunD groups (only at −300 pA), indicative of reduced I_h. *p < 0.05, **p < 0.01 (two-way ANOVAs; Holm–Sidak comparisons). G, H, Mean maximal negative current and voltage (produced by maximal negative current), respectively, in GFP, ΔFosB, and ΔJunD cells. No differences were observed between groups; p > 0.05 (one-way ANOVA). I, Difference between peak and S.S. at maximal negative current across groups. ΔFosB significantly decreased the difference compared with GFP; **p < 0.01 (one-way ANOVA; Holm–Sidak comparisons). J, Sag ratio (S.S./peak at maximal negative current ratio) across groups. ΔFosB significantly increased the sag ratio (decreased I_h) compared with GFP; *p < 0.05 (one-way ANOVA; Holm–Sidak comparisons). All graphs display means ± SEM.

ΔFosB decreases spontaneous EPSC amplitude. A, Representative traces (−80 mV) showing sEPSCs in hippocampal CA1 neurons expressing GFP (n = 20 cells; n = 7 mice), ΔFosB (n = 16 cells; n = 6 mice), and ΔJunD (n = 9 cells; n = 5 mice). B, sEPSC frequency (in Hz) across groups. No differences in sEPSC frequency were observed. C, sEPSC peak amplitude (in pA) across groups. Both ΔFosB and ΔJunD reduced sEPSC amplitude compared with GFP; *p < 0.05 (one-way ANOVA; Holm–Sidak comparisons). D, Cumulative fraction of the peak amplitudes (5–30 pA) across groups. Both ΔFosB and ΔJunD were shifted to the left from GFP. All graphs display means ± SEM.