A high-throughput all-optical platform for mapping gene perturbations to electrophysiology

An engineered hiPSC line enabling all-optical voltage imaging maps knockdowns of five sodium- and potassium-channel genes to distinct electrophysiological phenotypes at high throughput.

• Why it matters: Electrical phenotyping limits how quickly gene perturbations can be linked to cellular function, especially across many targets.
• What they did: The platform combines wide-field voltage imaging with inducible NGN2, CRISPR interference, and degron-gated Voltron2 and CheRiff in hiPSC-derived neurons, recording ~1,500 spiking glutamatergic neurons at 800 Hz (or ~3,000 at 660 Hz) and extracting single-cell voltage features.
• The result: Arrayed knockdown of five sodium- and potassium-channel genes yields distinct firing patterns, action-potential waveforms, and subthreshold dynamics, supporting scalable functional genomics in hiPSC-derived cells.

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