Fig. 3: High-frequency STN DBS causes sustained inhibition in local neurotransmitter release in the STN of normal mice.
From: Differential synaptic depression mediates the therapeutic effect of deep brain stimulation
a,g,m, Schematic illustrations showing microinjection of AAVs to express yellow glutamate sensor SF-Venus-iGluSnFR.S72A with tdTomato (a) and green GABA sensor iGABASnFR.F102G with tdTomato (g) and to co-express SF-Venus-iGluSnFR.S72A and iGABASnFR.F102G with tdTomato (m) in STN neurons. b,h,n, Representative images to show the expression of SF-Venus-iGluSnFR.S72A and tdTomato (b), iGABASnFR.F102G and tdTomato (h) and SF-Venus-iGluSnFR.S72A, iGABASnFR.F102G and tdTomato (n) in STN neurons. Scale bars, 200 μm. c,i,o, Illustrations of fiber photometry recordings of local glutamate release (c), GABA release (i) and simultaneous recording of glutamate and GABA release (o) using ratiometric fluorescence measurement of fluorescent sensors co-expressed with control fluorescent protein tdTomato. d,j, Representative emission spectra of SF-Venus-iGluSnFR.S72A and tdTomato (d) and iGABASnFR.F102G and tdTomato (j) expressed by STN neurons before and during DBS stimulation. e,k,q, Time-lapsed fluorescence ratio of SF-Venus-iGluSnFR.S72A/tdTomato (e), iGABASnFR.F102G/tdTomato (k) and SF-Venus- iGluSnFR.S72A/tdTomato and iGABASnFR.F102G/tdTomato recorded simultaneously from the same mice (q), normalized to the baseline before the first DBS stimulation, to show the DBS-induced changes in local glutamate and GABA release. f,l, Summary of DBS-induced changes in local glutamate (f) and GABA release (l) in the STN at different stimulation intensities. *P < 0.05 (for f: 100 µA versus 150 µA, P = 0.0186; 150 µA versus 200 µA, P = 0.0483; for l: 100 µA versus 150 µA, P= 0.0370), n = 7 mice for Venus-iGluSnFR group and n = 6 mice for iGABASnFR group, including both males and females, repeated one-way ANOVA followed by Dunnett’s multiple comparisons test. p, Representative emission spectrum (black) recorded from a mouse co-expressing SF-Venus-iGluSnFR.S72A, iGABASnFR.F102G and tdTomato in STN neurons (normalized by tdTomato emission peak), overlaid with normalized reference emission spectra of SF-Venus-iGluSnFR.S72A (yellow), iGABASnFR.F102G (green) and tdTomato (red). r, Comparison of DBS-induced changes between glutamate and GABA release at different stimulation intensities, recorded from mice co-expressing SF-Venus-iGluSnFR.S72A, iGABASnFR.F102G and tdTomato. **P < 0.01, ***P < 0.001 (100 µA: P = 0.0013, 150 µA: P = 0.0009, 200 µA: P = 0.0088), n = 8 mice, including both males and females, paired two-tailed t-test.
