Fig. 6: Tonic nRE stimulation rescues anesthesia-induced impairments of working memory and short-term synaptic plasticity in fAD mice.

a Experimental design. SWM-T spatial working memory test; GA general anesthesia. b Temporal dynamics of fAD mice’s SWM pre- and post-tDBS-nRE for 60 s delay (n = 8) (P = 0.0098 for day 0 after GA, Sidak’s multiple comparisons). c GA-induced SWM impairments rescued by tDBS-nRE (P = 0.0001, mixed-effect analysis, Sidak’s multiple comparisons: 60 s delay: P = 0.0021, 0.0306, 0.7189 for baseline vs. 1st GA, GA1 vs. GA2, baseline vs. 2nd GA, respectively (n = 8). 90 s delay: P = 0.0040, 0.0005, 0.7774 for the same comparison groups, n = 7). d Temporal dynamics of fAD mice’s SWM after 1st (red) and 2nd (purple) GA session for 60 s delay (n = 6). e GA induced similar SWM impairments in 1st and 2nd anesthesia sessions (P = 0.0001, mixed-effect analysis, Sidak’s multiple comparisons. 60 s delay: P = 0.1104, 0.1547, 0.0114 for baseline vs. 1st GA, GA1 vs. GA2, and baseline vs. 2nd GA; n = 6; 90 s delay: P = 0.0114, 0.1051, 0.0004 for the same comparison groups; n = 6). f–g Lower IES rates in CA1 (f, P = 0.0078, Wilcoxon two-tailed test, n = 8) and mPFC (g, P = 0.0469, Wilcoxon two-tailed test, n = 7) after tDBS-nRE. h No change in burst-suppression ratio (BSR) after tDBS-nRE (n = 7, P = 0.9669, Wilcoxon two-tailed test). i Paired-pulse ratio in nRE-CA1 pathway of WT (n = 5; 3 males, 2 females), fAD (n = 9; 6 males, 3 females), and fAD+tDBS-nRE (n = 5; 3 males, 2 females) for 3 days post-GA, normalized to baseline (P = 0.0001, one-way ANOVA, Sidak’s multiple comparisons: WT vs. fAD P = 0.0004, fAD +tDBS vs. fAD P = 0.0011, WT vs. fAD+tDBS P = 0.9522). j Representative fEPSP traces in nRE-CA1 synapses during baseline (dashed line) and 24 hr post-GA, before (red) and after (green) tDBS-nRE. Scale bars: 0.2 mA, 30 ms. k Paired-pulse ratio in nRE-CA1 pathway of fAD mice during baseline and 4 days post-GA before (red) and after (green) tDBS (n = 5). Error bars represent SEM; ns non-significant, *P < 0.05, **P < 0.01, ***P < 0.001.