Fig. 7
The genetic defects altered neuronal communication associated with neurosteroid Allopregnanolone. a, b Representative images and quantifications of neurosteroid allopregnanolone detected in 6–10-month-old HC (n = 9) and dCOs (PRNPE200K1, PRNPE200K2, T21, LRRK2G2019S; n = 4). Scale bar is 100 µm. c Burst rate before and after treatments with 1 µM pregnanolone (n = 10 for the HC; n = 8 for the other organoid lines). d Relative intracellular calcium levels measured before and after treatments with either 1 µM pregnanolone or 5 μM nimodipine (n = 4 per an organoid line). e Burst rate before and after the treatments with 5 µM nimodipine (n = 4 per an organoid line). f, g The modulation index of the coupling between the delta/theta phases and the amplitudes of the upper gamma oscillations after treatments with pregnanolone (f; n = 4) and nimodipine (g; n = 4). b Allopregnanolone levels were compared between groups by One-way ANOVA with Dunnett’s correction for multiple comparisons. c, e Effect of the treatments within an organoid line was analysed by Paired Student’s t test. d Calcium levels after treatments were normalized to the pre-treatment levels and the effect of the treatments on the calcium flux was determined by One-sample t-test based on a hypothetical value of 1. f, g Measurements were analysed by Two-way ANOVA with Dunnett’s correction for multiple comparisons. Each point on the graphs represents an individual organoid. If not otherwise indicated CO colour code are as follows; HC (blue), PRNPE200K−1 (red), PRNPE200K−2 (yellow), T21 (purple) and LRRK2G2019S (grey). Bars and error denote mean and SEM. * p < 0.05, **p < 0.01, ***p < 0.001