Optoacoustic brains stimulation at submillimeter spatial precision

Low-intensity ultrasound is an emerging modality for neuromodulation. Yet, piezo-based transducers offer poor spatial confinement of excitation volume, often bigger than a few millimeters in diameter. In addition, the bulky size limits their implementation in a wearable setting and prevents integration with other experimental modalities. Here, we report spatially confined optoacoustic neural stimulation through a novel miniaturized Fiber-Optoacoustic Converter (FOC). The FOC has a diameter of 600 μm and generates omnidirectional ultrasound wave locally at the fiber tip through the optoacoustic effect. We show that the optoacoustic wave can directly activate individual cultured neurons and generate intracellular Ca 2+ transients. The FOC activates neurons within a radius of 500 μm around the fiber tip, delivering superior spatial resolution over conventional piezo-based low-frequency transducers. Combining FOC with electrophysiology, direct and spatially confined neural stimulation of mouse brain is achieved in vivo.