Fig. 2: GABAergic synaptic transmission plays a dominant role in DBS.

a Schematic showing whole-cell recording (with normal pipette solution) with local electric stimulation in STN slices of DD mice. Middle and bottom, example current-clamp recording showing the effects of HFS (b) and LFS (c) on spontaneous firing of STN neurons. Top, plots of the instantaneous frequency of APs and its coefficient of variation (CV, bin size: 1 s). Time windows (4 s) before, during, and after the stimulation were shown for data analysis in (f). d Group data showing changes in the firing rates in response to HFS and LFS over time (n = 8 neurons from 5 mice). Gray indicates the stimulation period. 130 vs. 20 Hz: paired t-test or Wilcoxon matched-pairs signed rank test, two-sided, 0–3 s, P < 0.01; 3–5 s, P < 0.05. e Comparing the firing rates within 10 s before, during, and after HFS (left) or LFS (right). Open circles indicate neurons with spontaneous firing (n = 5), while filled circles represent those with a holding current of 20–50 pA to maintain stable firing (n = 3). 130 Hz: Pre vs. Stim (P = 0.0156), 20 Hz: Pre vs. Stim (P = 0.7422), Wilcoxon matched-pairs signed rank test, two-sided. f Plots of the instantaneous frequency CV in the time windows shown in (b) (n = 8 neurons from 5 mice). 130 Hz Base vs. Intra-1 (P = 0.0005), Base vs. Intra−2 (P = 0.0016). 20 Hz Base vs. Intra-1 (P = 0.6933), Base vs. Intra−2 (P = 0.8860), paired t-test, two-sided. Data are represented as mean ± SEM. (g) Left, schematic of STN DBS with bilateral drug administration in DD mice. Right, a representative sagittal section (n = 4 mice) showing the position of cannula and electrode. Note that CTB-488 signals are restricted to the STN. Scale bar, 1 mm. h Representative changes in locomotion velocity within 60 s in response to STN DBS at 130 Hz before and 20 min after bilateral vehicle or bicuculline (BCC, 500 μmol, i.e., 1 μl with a concentration of 500 μM) administration to the STN. i, j Group data comparing the effects of DBS at 130 or 20 Hz on locomotion velocity before and after vehicle and BCC administration (n = 5 mice). For (i) 130 Hz Ctrl: Pre vs. Stim (P = 0.0052); Vehicle: Pre vs. Stim (P = 0.0011), paired t-test, two-sided. 20 Hz Ctrl: Pre vs. Stim (P = 0.1875), Vehicle: Pre vs. Stim (P = 0.4375), Wilcoxon matched-pairs signed rank test, two-sided. For (j) 130 Hz Ctrl: Pre vs. Stim (P = 0.0052), BCC: Pre vs. Stim (P = 0.8127), paired t-test, two-sided. 20 Hz Ctrl: Pre vs. Stim (P = 0.0685), paired t-test, two-sided; BCC: Pre vs. Stim (P = 0.3125), Wilcoxon matched-pairs signed rank test, two-sided. NS, not significant; *P < 0.05, **P < 0.01, ***P < 0.001. Source data are provided as a Source Data file. See also Supplementary Figs. 2–4.