Figure 4. Electrical recording of human brain organoids during early development.

a, Schematics of the stepwise assembly of mesh nanoelectronics with hiPSCs for cyborg brain organoids. b, Raw voltage traces at 1, 2, and 3 months after cortical differentiation c, Spectrograms at 1, 2, and 3 months of differentiation for channel 3 showing a strong increase in power between 0 to 1 kHz after 3 months of differentiation. * Denotes voltage artifacts. d, Corresponding power spectrums to (c). e, Signal power at 300 Hz for electrodes with detected neural activity. f, Normalized phase plot of single-unit action potentials and its corresponding waveforms (inset) detected from the same channel at 2 and 3 months of differentiation, showing an increase in the rate of depolarization. g-h, FWHm of depolarization (g), and spike count per neurons per 2-min recording (h) at 1, 2, and 3 months of differentiation. i, Spiking rate per neuron detected as a function of the inverse of the FWHm of depolarization, showing that the single-cell action potential spikes from neurons evolve towards shorter spike width and higher spiking rate over the time course of brain organoid development. In panels (e, g), value=mean ± S.D., ** P<0.01, one-way ANOVA with “Month 1” group as control. j, Injection of bicuculline (BCC) produces a significant increase in the spiking rate of signals detected by multiple electrodes. k, Injection of CNQX and D-AP5 produces a significant decrease in spiking rate of signals detected by multiple electrodes (n = 4 electrodes including data from p = 2 different cyborg brain organoids, bar plots show mean ± S.D.). * P<0.05, two-tailed, paired t-test.