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. 2024 Dec 5;10:184. doi: 10.1038/s41378-024-00817-y

Fig. 4. Supra- and sub-threshold intracellular-like recordings from outgrowth of induced pluripotent stem cell-derived brain organoids.

Fig. 4

a Schematic showing coating protocol for seeding iPSC-derived brain organoids on NEAs, as well as inset with schematic of targeted ion channels during pharmacological interrogation. Created in BioRender. Lab, B. (2023) B. b Brightfield image of brain organoids seeded on top of an NEA. c Representative 200 s-long trace showing spontaneous intracellular-like signals from a single channel (n = 2 separate seeding experiments with 3 devices per seeding round). d Zoomed-in trace showing representative supra-threshold “action potentials” and sub-threshold potentials. e Frequency spectrogram used to validate intracellular-like signals and discern supra- (> 100 Hz) and sub-threshold potentials (<100 Hz). Recording before (f), and after (g) TTX addition to the media (n = 2 devices). h Histogram summarizing all collected brain organoid spikes, showing putative quantization of subthreshold potentials (N = 103). (i) Bright field image showing organoids on an NEA, with intracellular recordings taken from overlying cells in (ii) and (iii) but no spiking from a bare electrode (i)