Fig. 7: Kremen1+ and Calb1+ dSPNs differentially regulate dopamine release.
From: Molecularly distinct striatonigral neuron subtypes differentially regulate locomotion
a Schematic of simultaneous fiber photometry and optogenetics to assess dopamine changes in the dorsal striatum in response to Kremen1+ and Calb1+ dSPN activation. b, c Representative images showing ChR2 (green), rDA3m (red), and TH (blue) in the dorsal striatum of Kremen12A-Cre (b) and Calb1IRES2-Cre (c) mice. Scale bar: 500 µm. d Dopamine signal changes during 20 Hz light stimulation of SN for varying durations in Kremen12A-Cre (top) and Calb1IRES2-Cre (bottom) mice. Solid traces with shade represent population mean ± SEM of ΔF/F changes aligned to stimulation onset. Light gray traces show mean ΔF/F changes for individual Kremen1- ChR2 (n = 9 mice) and Calb1- ChR2 (n = 10 mice) mice, with YFP group (Kremen1-YFP, n = 3 mice; Calb1-YFP, n = 3 mice). Same mouse dataset was used for further analysis in (e–g). e Initial dopamine elevation amplitudes following Calb1+ dSPNs activation compared to YFP controls. Two-way ANOVA: activation effect F(1,42) = 19.44, ****p = 7.1e-5; duration effect F(2,42) = 0.4331, p = 0.6513; interaction effect F(2,42) = 0.4730, p = 0.6264. Multiple comparisons: 5 s, *p = 0.0258; 15 s, *p = 0.0102. f, g Maximum dopamine reduction amplitudes (f) and post-stimulation (post-stim) dopamine release changes (g) following activation of Kremen1+ and Calb1+ dSPNs compared to YFP controls. f Two-way ANOVA: activation effect F (2,66) = 54.47, ****p = 1.1e-14; duration effect F(2,66) = 4.723, *p = 0.0121; interaction effect F(4,66) = 1.575, p = 0.1914. Multiple comparisons, Kremen1-ChR2 vs. Calb1-ChR2: 2 s, ** p = 0.0025; 5 s, **** p = 1.95e-6; 15 s, **** p = 3.3e-6; Kremen1-ChR2 vs. YFP: 2 s, ** p = 0.0087; 5 s, **** p = 9.2e-9; 15 s, **** p = 1.12e-8. g Two-way ANOVA: activation effect F(2,66) = 21.66, ****p = 5.9e-8; duration effect F(2,66) = 0.5153, p = 0.5997; interaction effect F(4,66) = 1.234, p = 0.3052. Multiple comparisons, Kremen1-ChR2 vs. Calb1-ChR2: 5 s, ** p = 0.0095; 15 s, **** p = 9.06e-6; Kremen1-ChR2 vs. YFP: 15 s, *** p = 0.0003. All data are represented as mean ± SEM.
