Fig. 1: HFS induces asynchronous release (AR) of neurotransmitter and alleviates movement deficit in DD mice. | Nature Communications

Fig. 1: HFS induces asynchronous release (AR) of neurotransmitter and alleviates movement deficit in DD mice.

From: Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release in mice

Fig. 1

a Schematic showing the injection of 6-OHDA into MFB to induce bilateral dopamine-depleted (DD) Parkinsonian mouse model, as well as bilateral DBS at the STN. b Top, a representative image (n = 6 mice) showing the absence of TH immunosignals in the dorsal striatum. Scale bar, 1 mm. Bottom, symbols indicate the stimulation sites at the STN in experiments shown in (d). c Representative behavior test showing increases in locomotion velocity in response to STN DBS at 130 Hz (high-frequency stimulation, HFS) but not at 20 Hz (low-frequency stimulation, LFS). d Group data comparing the average velocity within 60 s before, during, and after the DBS in DD mice (n = 12 mice). 130 Hz Pre vs. Stim (P = 0.0005), 20 Hz Pre vs. Stim (P = 0.4697), Wilcoxon matched-pairs signed rank test, two-sided. e Schematic showing local electric stimulation and IPSC recording with high-Cl- pipette solution in STN slices of DD mice. f Representative current traces (with stimulation artifacts removed) of IPSCs evoked by long-lasting trains (30 s) of HFS or LFS. SR and AR events can be clearly identified in traces with HFS. Red arrowheads indicate AR events. Few AR events can be detected in traces with LFS. Insets, expanded traces for clarity. g Gray, overlaid current traces before the stimulation onset (−2 to 0 s) and those evoked by individual electric pulses during indicated time periods of stimulation (2 s each). Blue, the average traces. Red arrowheads indicate AR events. h–k Group data showing changes in the total charge, SR charge, AR ratio (AR charge to total charge), and basal current of the evoked IPSCs during the HFS and LFS (bin size, 1 s; n = 9 neurons from 4 mice). Gray, time points with significant differences. Paired t-test or Wilcoxon matched-pairs signed rank test for (h, i) (two-sided): 130 vs. 20 Hz in (h) 0–9 s P < 0.01, 12–14 s P < 0.05; in (i) 0–5 and 7–8 s P < 0.05. For j, 130 vs. 20 Hz: two-way ANOVA without adjustments, P = 0.0022; changes over time: 130 Hz (P > 0.9999), 20 Hz (P = 0.9246), one-way ANOVA without adjustments. For (k) 130 vs. 20 Hz (P = 0.0008), two-way ANOVA without adjustments. l Group data comparing the AR ratio of IPSCs evoked by 130 and 20 Hz stimulation in control (n = 11 neurons from 4 mice) and DD mice (n = 9 neurons from 4 mice). DD: 130 vs. 20 Hz, paired t-test, two-sided, P = 0.0006; Ctrl: 130 vs. 20 Hz, paired t-test, two-sided, P < 0.0001; Ctrl vs. DD, 130 Hz: P = 0.0247, 20 Hz: P = 0.2706, unpaired t-test, two-sided. m Similar to (d) but with the same charge size of DBS (1200 pulses) in both HFS and LFS (n = 7 mice). 130 Hz, Pre vs. Stim (P = 0.0032), paired t-test, two-sided; 20 Hz, Pre vs. Stim (P = 0.1094), Wilcoxon matched-pairs signed rank test, two-sided. n–q Similar to (h–k) but with the same stimulation charge size (bin size, 40 stimulation pluses; n = 10 neurons from 4 mice). 130 vs. 20 Hz, two-way ANOVA without adjustments. n P = 0.0124; o P = 0.0017; p P = 0.0024; q P = 0.0010. Data are represented as mean ± SEM. 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. 1 and 4.

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