Fig. 7: LFS of PV axons also produces beneficial effect when AR strength is enhanced. | Nature Communications

Fig. 7: LFS of PV axons also produces beneficial effect when AR strength is enhanced.

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

Fig. 7

a Schematic of bilateral virus injections for selective expression of shRNA (Syt1) and oChIEF in GPe PV neurons and IPSC recording from STN slices of DD mice. b Representative current traces of IPSCs evoked by long-lasting trains of optic HFS or LFS with Syt1 down-regulation. Insets, expanded traces for clarity. c–f Group data showing changes in the total charge, SR charge, AR ratio, and basal current of the evoked IPSCs during optic HFS or LFS with Syt1 KD (n = 9 neurons from 4 mice). Gray, time points with significant differences. Paired t-test or Wilcoxon matched-pairs signed rank test for (c, d) (two-sided): 130 vs. 20 Hz in (c) 0 ~ 4 s, P < 0.05; in (d) 0 ~ 1 s, P = 0.0039. For (e) (P = 0.1415) and (f) (P = 0.0094), 130 vs. 20 Hz, two-way ANOVA without adjustments. g Group data comparing the AR ratio of IPSCs in control (data from Fig. 5e, n = 15 neurons from 8 mice) and Syt1 KD mice (n = 9 neurons from 4 mice). Ctrl: 130 vs. 20 Hz (P < 0.0001); KD: 130 vs. 20 Hz (P = 0.2267), paired t-test, two-sided. Ctrl-130 vs. KD-130 (P = 0.7797), Ctrl-20 vs. KD-20 (P = 0.0306), unpaired t-test, two-sided. h Schematic of virus injections for selective expression of Syt1 shRNA, or its non-specific control (NC) shRNA, with oChIEF in GPe PV neurons and bilateral optic fiber implantation in STN of DD mice. Representative behavior test showing increases in locomotion velocity in response to optic stimulation in mice with selective expression of the NC shRNA (i) or with Syt1 KD (j) in GPe PV cells. k Group data comparing the average velocity within 30 s before, during, and after the optic stimulation with the NC shRNA (n = 8 mice). Only HFS produced an increase in velocity, but not LFS. 130 Hz: Pre vs. Stim (P = 0.0039); 20 Hz: Pre vs. Stim (P = 0.2747), paired t-test, two-sided. l Similar to (k) but with Syt1 KD. Note the locomotion velocity increases during both HFS and LFS (n = 10 mice). 130 Hz: Pre vs. Stim (P = 0.0001); 20 Hz: Pre vs. Stim (P = 0.0010), paired t-test, two-sided. m, Group data comparing the ratio of locomotion velocity during stimulation (Stim) to that before stimulation (Pre) (NC, n = 8 mice; KD, n = 10 mice). NC-130 vs. NC-20 (P = 0.0092), KD-130 vs. KD-20 (P = 0.8695), paired t-test, two-sided. NC-130 vs. KD-130 (P = 0.4627), NC-20 vs. KD-20 (P = 0.0185), unpaired t-test, two-sided. 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.

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