Fig. 5: Direct effect of metformin and the requirement of AMPK activity in elevating the excitability of inhibitory interneurons and their outputs to pyramidal cells in the mPFC.

a APs recorded from mPFC pyramidal neurons of mouse brain slices and (b) fluorescence-labeled GABAergic interneurons from GAD1-GFP mouse brain slices in the presence of ACSF (baseline) or 10 µM metformin. Representative traces of APs (left) and AP firing (right), n = 6–9 cells from 4 mice. c Representative traces of APs from GABAergic neurons in the baseline, 20 μM Compound C (CC) and 10 μM metformin perfusion, and AP firings (right), n = 7 cells from 3 mice. In (a–c), two-way ANOVA followed by Tukey’s post hoc test. d Representative traces of sEPSCs (left) from pyramidal neurons at baseline or after 10 µM metformin perfusion and the statistical amplitude (middle) and frequency (right). e Representative traces of sIPSCs (left) from pyramidal neurons and the statistical amplitude (middle) and frequency (right). In (d, e), a pair-paired t test was used. f Representative traces of sIPSCs (left) in baseline, CC, CC + metformin perfusion, and the statistical amplitude (middle), the frequency (right), n = 6–9 cells from 4 mice, one-way ANOVA followed by Dunnett’s post hoc test. *P < 0.05; **P < 0.01.