Membrane deflection due to ultrasound results in cellular depolarization

Stimulating neural activity currently uses electrical, optical or chemical techniques. They are either invasive or have poor spatiotemporal resolution. Megahertz-order ultrasound noninvasively improves the resolution of neural stimulation and sonogenetic techniques improve sensitivity. However, the mechanism tying ultrasound to neural activity is poorly understood. The few models of the phenomenon to date have intrinsic errors. Experiments so far lack sufficient imaging speed to resolve the phenomena. We have developed a model that predicts membrane deflection due to an ultrasound stimulus, and verified the results of this model with novel measurements of the membrane's motion using high-speed digital holographic microscopy. Our experiments reveal that neuronal membranes can deflect by as much as 150 nm. We have used single neuron current clamp electrophysiology to verify transmembrane voltage changes predicted by the model. Our results form the foundation of our work in developing ultrasound-based neuromodulation devices for freely-moving mice and further exploration into sonogenetic tools for communication, diagnostics, and disease treatment.