Fig. 5: HFS of PV axons triggers AR, inhibits, and desynchronizes firing of STN neurons in vitro.

a Schematic showing optogenetic stimulation of PV axons from GPe and IPSC recording with high-Cl^- pipette solution in STN slices of DD mice. b Representative current traces of IPSCs evoked by long-lasting trains of optogenetic HFS (130 Hz) or LFS (20 Hz), similar to experiments with electric stimulation shown in Fig. 1. Red arrowheads indicate AR events. Note that robust AR events occurred during optic HFS. c–f Group data showing changes in the total charge, SR charge, AR ratio, and basal current of the evoked IPSCs during the optic HFS and LFS (n = 15 neurons from 8 mice). Gray, time points with significant differences. For (c) 130 vs. 20 Hz, 0–7 s, P < 0.05; for (d) 0–2 and 8–30 s, P < 0.05, Wilcoxon matched-pairs signed rank test, two-sided. For (e, f) 130 vs. 20 Hz, P < 0.0001, two-way ANOVA without adjustments. g Gray, overlaid current traces before the stimulation onset (−2 to 0 s) and those evoked by individual optic pulses during indicated time periods of stimulation (2 s each). Blue, the average traces. Red arrowheads indicate AR events. h, Examination of the effect of optic stimulation on firing rates of STN neurons (with normal pipette solution) with a more physiological level of Ca²⁺ (1.2 mM) and Mg²⁺ (1 mM) in the bath. Example current-clamp recording showing the effects of optogenetic HFS (i) and LFS (j) on spontaneous firing of STN neurons. Top, plots of the instantaneous frequency of APs and its CV (bin size: 1 s). Time windows (4 s) before, during, and after the stimulation were shown for data analysis in (m). k Group data showing changes in the firing rates in response to optogenetic HFS and LFS over time (n = 5 neurons from 3 mice). Gray indicates the stimulation period. 130 vs. 20 Hz, Wilcoxon matched-pairs signed rank test or paired t-test, two-sided, 1–3 s, P < 0.05. l Comparing the firing rates within 10 s before, during, and after optogenetic HFS (left) or LFS (right). Open circles indicate neurons with spontaneous firing (n = 4), while filled circles represent those with a holding current of 50 pA to maintain stable firing. 130 Hz: Pre vs. Stim (P = 0.0058); 20 Hz: Pre vs. Stim (P = 0.0301), paired t-test, two-sided. m Plots of the instantaneous frequency CV in the time windows shown in (i) (n = 5 neurons from 3 mice). 130 Hz: Base vs. Intra-1 (P = 0.0101), Base vs. Intra−2 (P = 0.0024); 20 Hz: Base vs. Intra-1 (P = 0.1377), Base vs. Intra−2 (P = 0.0527), paired t-test, two-sided. NS, not significant; *P < 0.05, **P < 0.01, ***P < 0.001. Data are mean ± SEM. Source data are provided as a Source Data file. See also Supplementary Fig. 6.