Fig. 6
T21 impaired NKCC1 activity and increased the activity of extra-synaptic GABARs. a, b Protein levels of NKCC1 and NKCC2 in 6–10-month-old HC (n = 6) and dCOs (PRNPE200K1 with n = 3, PRNPE200K2with n = 5, T21 with n = 4, and LRRK2G2019S with n = 4). Representative images are in Additional file 17. c Burst rate in response to a treatment with 10 µM NKCC1 blocker bumetanide (n = 4 per an organoid line). d Representative images of surface GABARs (green) before and after treatments with GABAR blockers (100 µM Bicuculine and 10 μM CGP55845 hydrochloride) or 500 μM ZnCl2 in HC and T21 organoids. Scale bar is 100 µm. e Quantifications of the levels of surface GABARs before and after treatments with either GABARs blockers or ZnCl2 (n = 4). f Burst rate before (n = 24 for the HC and n = 16 for the other organoid lines) and after exposure to 500 μM ZnCl2 (n = 6 for the HC and n = 4 for the other organoid lines). c–f Average burst rates and levels of surface GABARs before and after the treatments with Bumetanide or ZnCl2 were compared by paired Student’s t-test. 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