Fig. 1
Neuronal firing and network communication at 3–4 and 6–10 months old. a Top panel: a picture of cerebral organoids on Multi-electrode arrays (MEA) with the black dots indicating the electrodes; Middle panel: a representative diagram of local field potential detected by each electrode shown in the top panel); Bottom panel: a diagram displaying how the raw data were processed. b Representative raster blots displaying neuronal firings or spikes (dots), bursts (clusters of dots), and network communication (depicted by electrodes with overlapping bursts) in the healthy controls (HC) and the organoids with genetic defects (PRNPE200K1, PRNPE200K2, T21, and LRRK2G2019S). c Spike rate (n = 18 to 20 at 3–4 months; n = 36 to 44 at 6–10 months). d Burst rate (n = 14 to 19 at 3 months; n = 50 at 6–10 months). e Periodicity of network firing (n = 18 to 20 at 3–4 months; n = 62 to 67 at 6–10 months). f Percentage of connected electrodes based on spike correlations (left panel; n = 8 to 11 at 3–4 months; n = 30 to 46 at 6–10 months) and overlapping bursts (right panel; n = 17 to 29 at 6–10 months). g Inter-spike interval coefficient of variation (CV; n = 18 to 20 at 3–4 months; n = 20 to 23 at 6–10 months). h Representative graphs of the connectivity between electrodes (nodes) based on the spike correlation with the node colour and size representing the burst rate and spike rate. c–f The parameters of neuronal spiking in the organoids with mutations were compared to the age-matched HC by One-way ANOVA on ranks with Dunnett’s correction for multiple comparisons. g Paired Student’s t-test on ranks was used to analyse the age-dependent change in the inter-spike interval CV. 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