Fig. 5

DA-Tsc1-KO mice have increased DA synthesis. a, b Confocal images of midbrain sections from DA-Tsc1-WT (a) and DA-Tsc1-KO (b) mice expressing a Cre-dependent tdTomato reporter in DA neurons, scale bars = 500 μm. c Mean ± SEM number of tdTomato-positive DA neurons, SNc and VTA combined. n = 3 mice per genotype, p = 0.4343, unpaired, two-tailed t test. d Representative Western blots for tyrosine hydroxylase (TH), vesicular monoamine transporter (VMAT-2), DARPP-32, and histone 3. e Mean ± SEM striatal protein content of TH and VMAT-2. n = 6 DA-Tsc1-WT and 9 DA-Tsc1-KO mice. *p = 0.0169, Welch’s two-tailed t test. f–i Low-magnification image (f, h, scale bars = 400 μm) and high-magnification image (g, i, from the boxed regions, scale bars = 50 μm) of the dorsolateral striatum from DA-Tsc1-WT (f, g) and DA-Tsc1-KO (h, i) mice showing TH immunostaining. j Mean ± SEM TH immunofluorescence intensity in the dorsolateral striatum. n = 6 mice per genotype. **p = 0.0055, paired two-tailed t test. k, l Images of SNc DA neurons from DA-Tsc1-WT (k) or DA-Tsc1-KO (l) mice immunostained for TH, scale bars = 25 μm. m Cumulative distributions of TH levels in SNc DA neurons (DA-Tsc1 WT: n = 759 neurons from three mice, DA-Tsc1 KO: n = 855 neurons from three mice). ****p < 0.0001, Kolmogorov–Smirnov test. n Dorsal striatum mean ± SEM total tissue content of DA and 3,4-dihydroxyphenylacetic acid (DOPAC). Ratio = DOPAC/DA per mouse. n = 6 mice per genotype, **p = 0.0043, unpaired, two-tailed t test. o–r Low-magnification image (o, q, scale bars = 400 μm) and high-magnification image (p, r, from the boxed regions, scale bars = 50 μm) of the ventral striatum from DA-Tsc1-WT (o, p) and DA-Tsc1-KO (q, r) mice showing TH immunostaining. s Mean ± SEM TH immunofluorescence intensity in the ventral striatum. n = 7 mice per genotype. *p = 0.0159, paired, two-tailed t test. t, u Confocal images of VTA DA neurons from DA-Tsc1-WT (t) or DA-Tsc1-KO (u) mice immunostained for TH, scale bars = 25 μm. v Cumulative distributions of TH levels in VTA DA neurons (DA-Tsc1 WT: n = 892 neurons from three mice, DA-Tsc1 KO: n = 863 neurons from three mice). ****p < 0.0001, Kolmogorov–Smirnov test. w Nucleus accumbens mean ± SEM total tissue content of DA and DOPAC. n = 6 mice per genotype. ***p = 0.0004, unpaired, two-tailed t test. For all bar graphs, dots represent values for individual mice. Source data are provided as a Source Data file.