Fig. 4: RSD induction specifically reduced mPFC GABAergic activity, and the rescue effect of oral metformin treatment was absent in AMPK KOmPFC mice.

a sEPSCs recorded from mPFC pyramidal neurons of RSD mice after metformin treatment. Example traces (top), and the statistical amplitude and the frequency (bottom), n = 19–23 cells from 6 mice. Veh, vehicle; Met, metformin. b sIPSCs recorded from mPFC pyramidal neurons of RSD mice after metformin treatment. Example traces (top) and the statistical amplitude and frequency (bottom); n = 41–58 cells from 6 mice. In (a, b), one-way ANOVA with Tukey’s test. c Action potentials (APs) from pyramidal neurons of WT mice and (d) from fluorescence-labeled GABAergic interneurons in GAD1-GFP mice subjected to RSD stress and metformin treatment, n = 11–18 cells from 3 to 4 mice. Two-way ANOVA followed by Tukey’s test. e sEPSCs recorded from mPFC pyramidal neurons of CA-AMPK mice after RSD stress. Example traces (top) and the statistical amplitude and frequency (bottom); n = 21–23 cells from 6 mice. f sIPSCs recorded from mPFC pyramidal neurons of CA-AMPK mice after RSD stress. Example traces (top) and the statistical amplitude and frequency (bottom), n = 20–25 cells from 6 mice. In (e, f), unpaired Student’s t tests were used. g The action potentials (APs) from GABAergic interneurons of CA-AMPK mice and AMPK-flox mice after RSD stress. All the cells patched were fluorescence-labeled GABAergic interneurons in GAD1-GFP mice subjected to virus transmission and RSD stress, n = 15–18 cells from 5 to 6 mice. h sEPSCs and (i) sIPSCs recorded from mPFC pyramidal neurons in AMPK Flox and AMPK KOmPFC mice (top) and the frequency and amplitude of sEPSCs/sIPSCs (bottom). In (e), n = 24–25 cells from 3 mice; in (f), n = 43–54 cells from 3 mice; unpaired Student’s t test. j sIPSCs recorded from mPFC pyramidal neurons of AMPK KOmPFC mice treated with metformin. Representative traces (left) and the amplitude and frequency of sIPSCs (right), n = 21–23 cells from 3 mice. One-way ANOVA with Tukey’s test. *P < 0.05; **P < 0.01.