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. 2022 Jul 4;11:e75253. doi: 10.7554/eLife.75253

Figure 4. Subthalamic nucleus deep brain stimulation (STN DBS) variably changes hyperdirect M1 neural activity.

(A) Left: Sagittal schematic showing STN DBS and M1-STN GCaMP fiber photometry. Right: Postmortem sagittal section showing GCaMP expression and estimated fiber placement in M1 (inset, scale = 500 μm). (B) Representative single-session velocity (black) and M1-STN GCaMP signal (green) in response to 60 Hz STN DBS. (C) Average velocity (top) and M1-STN GCaMP signal (bottom) before, during, and after 60 Hz STN DBS (N=9 mice). (D) Representative single-session velocity (black) and M1-STN GCaMP signal (green) in response to 100 Hz STN DBS. (E) Average velocity (top) and M1-STN GCaMP signal (bottom) before, during, and after 100 Hz STN DBS (N=8 mice). Statistical significance was determined using a one-way repeated measures ANOVA with a Tukey HSD post hoc analysis applied to correct for multiple comparisons; ***p < 0.001 (only comparison between pre and stim shown, see Supplementary file 1, table 1 for detailed statistics). Arrowhead in velocity and GCaMP traces corresponds to 1 cm/s and 0 z-score, respectively. Bar plots show mean ± SEM.

Figure 4.

Figure 4—figure supplement 1. STN DBS drives variable and slow changes in hyperdirect M1 activity.

Figure 4—figure supplement 1.

(A) Sagittal schematic showing estimated extent of viral AAV-retro and GCaMP6s spread in the subthalamic nucleus (STN) and M1, respectively, of wild-type (WT) mice (N=9 mice). (B) Postmortem sagittal section example showing AAV-retro expression in the STN (red), resulting in GCaMP6s expression in M1 neurons (green) projecting to the STN and cerebral peduncle (cp). (C–D) Average velocity over time (black) and M1-STN GCaMP signal (green) following 60 Hz STN DBS (C, N=9 mice) or 100 Hz STN DBS (D, N=8 mice). (E) Average movement velocity (top) and M1-STN GCaMP signal (bottom) during deep brain stimulation (DBS) sessions grouped by stimulation frequency: Low = 5–40 Hz, Med = 60–100 Hz, High = 120–180 Hz stimulation. (F) Scatter plot comparing hyperdirect M1 photometry signal to movement velocity during 60 Hz STN DBS (each dot represents average for one mouse, N=9 mice). (G) Sagittal schematic showing estimated extent of M1 lesions in WT mice (N=11 mice). Statistical significance was determined using a one-way ANOVA (see Supplementary file 1, table 1 for detailed statistics). Arrowhead in velocity traces and GCaMP traces corresponds to 1 cm/s and 0 z-score, respectively. Velocity and GCaMP traces show mean ± SEM.