Fig. 10: Genetic knockdown of Gabbr1 receptor affects Kremen1⁺ dSPN-induced alterations in Aldh1a1⁺ DAN activity.

a Schematic illustrating simultaneous fiber photometry recording of Aldh1a1⁺ DAN activity and optical activation of Kremen1⁺ dSPNs in Aldh1a1⁺ DAN-specific Gabbr1 control (Ctrl) and knockdown (KD) mice. b Representative images showing ChR2 (red), GCaMP8s (green), ALDH1A1 (magenta) and TH (blue) staining in the Str of Kremen1^2A-Cre;Aldh1a1^CreERT2 double KI mice. Optical fiber locations in the striatum and SN are indicated. Scale bars: 500 µm (Str) and 100 µm (SN). c Changes in GCaMP8s signals in the Aldh1a1⁺ DAN axon terminals in the dStr during 20 Hz light stimulation at varying durations of Kremen1⁺ dSPN activation in the SN under Gabbr1-KD (red) and Ctrl (brown) conditions. Data are presented as mean of each group of mice (solid line) ± SEM (shaded area). n = 6 mice per each group. d Amplitude of Aldh1a1⁺ DAN activity reduction following activation of Kremen1⁺ dSPNs in KD and Ctrl conditions. n = 6 mice per group. Two-way ANOVA: stimulation duration effect, F(2, 30) = 1.202, p = 0.3147; genotype effect, F(1, 30) = 15, ^***p = 0.0005; interaction effect, F(2, 30) = 0.3312, p = 0.72. Multiple comparisons test: ^*p = 0.024. e Post-stimulation rebound of Aldh1a1⁺ DAN activity following activation of Kremen1⁺ dSPNs in KD and Ctrl conditions. n = 6 mice per group. Two-way ANOVA: stimulation duration effect, F(2, 30) = 4.4651, ^*p = 0.02; genotype effect: F(1, 30) = 12.20, ^**p = 0.0015; interaction effect, F(2, 30) = 1.408, p = 0.26. Multiple comparisons test: ^*p = 0.0185. All error bars are represented as mean ± SEM. f The schematic summary illustrates that Calb1⁺ SPNs promote locomotion, whereas Kremen1⁺ SPNs terminate ongoing movement by inhibiting the activity of Aldh1a1⁺ DANs via GABBR1 receptors.