Fig. 1

Prefrontal tDCS enhances hippocampal DA outflow via activation of VTA neurons in 7-month-old Tg2576 mice. a Schematic representation of the experimental timeline: Tg2576 and WT mice (7- or 12-month-old) were implanted with prefrontal cannulae, followed by a 2-day recovery period. Mice then received either daily tDCS (20 min/day, 5 days/week) or Sham stimulation for two consecutive weeks (for c-Fos analysis, a single session of tDCS or Sham stimulation was administered under isoflurane anaesthesia, and 7-month-old animals were sacrificed 1 hour post-stimulation). After 2 more days of recovery, 7-month-old mice underwent subsequent behavioural or neurophysiological experiments. 12-month-old mice were used only for neuroinflammation and plaque analysis. b Representative coronal section and confocal images of the VTA (upper panel) and LC (bottom panel) showing c-Fos (red) labelled nuclei of TH+ neurons (green) of 7-month-old Tg Sham and Tg tDCS mice (scale bar: 10 μm). Plots show the percentage of c-Fos+/TH+ neurons within the VTA or the LC (n = 3 mice/group; VTA: unpaired t-test: **p = 0.0047). c-e Schematic representation of in vivo microdialysis setup for measuring neurotransmitter release. Plots show basal and KCl-induced hippocampal DA (d) and NE (e) levels in 7-month-old WT Sham (n = 4 males), WT tDCS (n = 4 males), Tg Sham (n = 4 males) and Tg tDCS (n = 6 males) mice measured at different time points (mean ± S.E.M.; d, 3-way RM-ANOVA: time × genotype × treatment, F4,56 = 0.7572, p = 0.5575; time, F4,56 = 16.60, p < 0.0001; genotype, F1,14 = 1.608, p = 0.2254; treatment, F1,14 = 4.785, p = 0.0462; Tg Sham Post KCl 1–Tg tDCS Post KCl 1 **p = 0.0014, WT tDCS Basal Mean–WT tDCS Post KCl 1 p = 0.0059, Tg tDCS Basal Mean–Tg tDCS Post KCl 1 p < 0.0001 all with Tukey’s post hoc test. e, 3-way RM-ANOVA: time × genotype × treatment, F4,48 = 0.1822, p = 0.9465; time, F4,48 = 26.24, p < 0.0001; genotype, F1,12 = 0.1302, p = 0.7245; treatment, F1,12 = 0.0500, p = 0.8268; Tg Sham Basal Mean–Tg Sham KCl p = 0.0118, Tg tDCS Basal Mean–Tg tDCS KCl p = 0.0003 both with Tukey’s post hoc test). In all figures, empty dots refer to female mice, while full dots to males. [Figure created using BioRender.com]