Extended Data Fig. 7: Neuronal spontaneous activity in SUV420H1^+/− and isogenic control organoids.

a, Left, Representative image of a PGP1 SUV420H1 organoid infected with SomaGCaMP6f2. Right, ΔF/F signal at the peak of a network burst. Scale bar: 100 μm. b, Heat map of calcium signal from individual cells (rows), showing the effect of 2 μM TTX. c, Top, representative trace of spontaneous calcium signal (corresponding to cell #3 in Fig. 1g). Bottom, high magnification traces of calcium transients, displaying the difference in amplitude between the isolated event and the network burst (top), and normalized traces (bottom) showing their kinetics and the multiple peaks of the burst signal. d, MEA recordings. Top, Spatial configuration of recording electrodes. Middle, example raw traces for the numbered electrodes shown at the top, and the effect upon 2 μM TTX application. Yellow columns indicate the network bursts. Right, individual (grey) and average (colour) spike waveforms for each electrode. High magnification of the trace #4 showing the individual spikes (asterisk) during a burst event. Bottom, average spike waveform (right) in a unit of electrodes (left), extracted at the time points determined by the spikes in electrode #4. e, f, Synchronous network activity in human brain organoids. Heat map of cross-correlation index (e) and cross-correlogram against a reference signal (cell #135) for a representative recording. As a control, the signal of 10 cells were circularly shifted by a random phase and the cross-correlation was then calculated. In f, the average value was plotted, and the synchronous activations as well as the periodic bursting can be seen (“All cells” in red). g, Effect of NBQX on neuronal activity. Representative traces for individual cells were normalized (3 traces for SUV420H1^+/− are superimposed) and post-NBQX residual/isolated calcium transients are indicated by asterisks. h, Effect of NBQX on calcium signal. Heat map of ΔF/F signal for 15 representative cells in control (top) and SUV420H1^+/− (bottom) organoids. i, j, Inter-spike interval (ISI) analysis for the network bursting. Relative frequency (top) and cumulative frequency distribution (bottom) of ISI for control and SUV420H1^+/− organoids. In j, two-sided Kolmogorov-Smirnov test (n = 5 organoids per genotype). Number of organoids used for each analysis can be found in the Methods under “Statistics and reproducibility”.