Fig. 5
The genetic defects altered the agonist-dependent activity of the major ionotropic receptors. a, c, e, g Burst rate recorded in 6–10-month-old HC and dCOs (PRNPE200K1, PRNPE200K2, T21, and LRRK2G2019S) before and after exposure to increasing concentrations of kainate (a; n = 4), AMPA (c; n = 4), NMDA (e; with 5 µM of glycine; n = 4), and GABA (g; n = 4). b, d, f, h Intracellular levels of calcium before and after exposure to increasing concentrations of kainate (b; n = 4-), AMPA (d; n = 4–7), NMDA (f; with 5 µM of glycine; n = 4–7), and GABA (h; n = 4). i–k Burst rate before and after treatments with 30 μM NBQX (i; n = 4), 100 μM AP5 and 10 µM maleate solution (j; n = 4), and 100 µm Bicuculine and 10 μM CGP55845 hydrochloride (k; n = 4). l Burst rate before and after stimulating the organoids with 500 μM NMDA/5 µM glycine in the presence of GABAR (GB) receptors blockers, 100 µM Bicuculine and 10 μM CGP55845 hydrochloride (n = 7 for the HC; n = 4 for other organoid lines). The dose- response (mean burst rate or intracellular calcium) to each treatment was compared between organoids by Repeated Measures Two-way ANOVA with Dunnett’s correction for multiple comparisons. i–l We used paired Student’s t-test to compare the average burst rate before and after treatments. 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, ****p < 0.0001. a–h Asterisk colour signifies which organoid line with the statistically significant results