Fig. 1: High-frequency STN DBS causes sustained inhibition in STN neurons after initial excitation in normal mice.
From: Differential synaptic depression mediates the therapeutic effect of deep brain stimulation
a, Schematic illustration showing microinjection of AAVs to express GCaMP6f and tdTomato in STN neurons in Vglut2-cre mice. b, Representative images to show the expression of GCaMP6f and tdTomato in the STN. Scale bar, 200 μm. c, A picture of a lab-made hybrid probe consisting of an optical fiber for photometry recordings and an electrode for monopolar DBS stimulation. The two indicator lines point to the gold connector pin soldered to the insulated tungsten wire, which serves as the cathode during monopolar DBS stimulation, and to the ceramic ferrule of the optical fiber probe, respectively. The electrode and fiber probe are secured together using Metabond dental adhesive. A schematic illustration of this electrode–optical fiber hybrid probe is shown in d. d, Schematic illustration of fiber photometry recordings during monopolar DBS stimulation in the STN in vivo. The hybrid probe shown in c is implanted to target the STN. A stainless steel wire secured to the anchoring screw on the skull serves as the anode during DBS. e, Illustration of fiber photometry recordings of postsynaptic neural activity in the STN during STN DBS using GCaMP6f and tdTomato co-expressed in STN neurons. tdTomato serves as a control fluorescent protein for ratiometric measurement of cytosolic Ca2+. f, Representative emission spectra of GCaMP6f and tdTomato recorded from STN neurons before and during DBS stimulation. g, Time-lapsed ratio of GCaMP6f/tdTomato fluorescence (normalized to the baseline before the first DBS stimulation) to show the DBS-induced responses in STN neurons at different stimulation intensities. h, Summary of DBS-induced decreases in the cytosolic Ca2+ in STN neurons at different stimulation intensities. *P < 0.05 (100 µA versus 150 µA, P = 0.0178; 150 µA versus 200 µA, P = 0.0153), n = 6 mice, including both males and females, repeated one-way ANOVA followed by Dunnett’s multiple comparisons test.
