Fig. 9: Knockdown of Gabbr1 receptors in Aldh1a1⁺ DANs abolishes Kremen1⁺ dSPN-induced locomotion alterations.

a Schematic showing selective activation of Kremen1⁺ dSPNs (K⁺dSPN, a) or Kremen1-negative dSPNs (K^-dSPN, f) and genetic deletion of Gabbr1 receptors (Gabbr1-KD) in Aldh1a1⁺ DANs in Kremen1^2A-Cre;Aldh1a1^CreERT2 double KI mice. b Representative images of ChR2 (green), TH (magenta) and DAPI (blue) in the dorsal striatum and SN. Scale bars: 500 µm (dStr) and 100 µm (SN). c Changes in instantaneous locomotion velocity (relative to the first 3-min baseline) during open-field test with K⁺dSPN activation under Gabbr1-KD and control (Ctrl) conditions. Gabbr1-KD: n = 11 mice; Ctrl: n = 8 mice, the same mouse dataset was used in (c–e). d Comparison of velocity changes between light-off and -on periods. Gabbr1-KD: t₍₁₀₎ = 0.72, paired t-test, two-tailed, p = 0.49. Ctrl (n = 8 mice): t₍₇₎ = 5.40, ^**p = 0.001. e Velocity changes during the 1^st Off and 2^nd Off periods in Gabbr1-KD and Ctrl. One sample t-test, two-tailed. Gabbr1-KD: 1^st Off, p = 0.32; 2^nd Off, p = 0.35. Ctrl: 1^st Off, ^*p = 0.045, 2^nd Off p = 0.27. g Representative images of ChR2 (green), MOR1 (magenta) in the dorsal stratum, and ChR2 (green), TH (magenta) in the SN. Scale bars: 500 µm (dStr) and 100 µm (SN). h Changes in instantaneous locomotion velocity (relative to the first 3-min baseline) during open-field test with K^–dSPN activation under Gabbr1-KD and Ctrl conditions. Gabbr1-KD: n = 8 mice, Ctrl: n = 8 mice, the same mouse dataset was used in (h–j). i Comparison of velocity changes between light-off and -on periods. Gabbr1-KD: t₍₇₎ = 4.11, paired t-test, two-tailed, ^**p = 0.0045. Ctrl: t₍₇₎ = 3.26, ^*p = 0.014. j Velocity changes during the 1^st Off and 2^nd Off periods in Gabbr1-KD and Ctrl mice. One sample t-test, two-tailed. Gabbr1-KD: 1^st Off, p = 0.54; 2^nd Off, ^**p = 0.0035. Ctrl: 1^st Off, ^*p = 0.035; 2^nd Off, ^***p = 0.0006. All error bars are presented as mean ± SEM. The data are presented as mean (solid line) ± SEM (shaded area) in velocity traces.