Fig. 2: Intracellular mechanisms of DBS inhibition of M1 pyramidal cells in rats.
From: Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms
a In vivo experimental set-up. b M1 pyramidal neurons recorded intracellularly display a decreased spontaneous activity (Wilcoxon signed-rank test, n = 20, p = 0.0002), and hyperpolarized membrane potential (p = 0.0007) during DBS (mean ± SEM and individual neurons); 95% were spontaneously active. c Pyramidal cell transfer function quantified with and without DBS. Depolarizing current steps (200 ms, 0–1.2 nA in 0.2 nA steps) were applied at 1 Hz before and during 100 s of DBS. DBS decreases evoked spiking activity. Left: raw data example and f–I relationship in a pyramidal neuron, showing a decreased evoked firing rate during DBS (DBS effect F1,90 = 155.72, p = 2.5 × 10−21, 2-way ANOVA followed by Bonferroni-corrected post-hoc tests: all p < 10−3 for 0.4–1 nA injected current). Right: DBS increases the rheobase (p = 0.0312, Wilcoxon signed-rank test, n = 17 neurons), without affecting the gain of the f–I curve (p = 0.1746, paired t-test) (mean ± SEM and individual neurons). Rheobase and gain were respectively determined as the x-intercept and the slope of the f-I curve after a linear fit. d Single-shock STN stimulation induces a pause in M1 pyramidal evoked firing. Top: representative trial and raster plot of current-evoked activity for 10 trials in the same neuron. Bottom: the interval between the STN stimulation and the next evoked-spike is longer than between the STN stimulation and the previous evoked spike (p = 0.0057, paired t-test, n = 6 neurons) (mean ± SEM and individual neurons). e Voltage-dependency of the potential evoked by single-shock STN stimulation. Left: a single-shock STN stimulation (red line) applied during hyperpolarizing or depolarizing current steps (−1.8 to +1.0 nA in 0.2 nA increments, mean of 10 trials) elicits an evoked potential (dashed line). Zoom of the PSP evoked by STN single stimulation for −1.6 nA injected current. The amplitude of the early phase of the PSP is inversely correlated with the membrane potential when the stimulation was applied (voltage-dependency of 9 individual neurons). Right: the STN-evoked potential reverses around −71.7 mV (n = 9 neurons) (mean ± SEM and individual neurons). DBS artifacts were removed in b, c for clarity. All statistical tests are two-tailed. *p < 0.05; **p < 0.005; ***p < 0.001.
