Neuromodulation with Submillimeter Spatial Precision by Optoacoustic Fiber Emitter

New techniques to non-invasively modulate neural activities with high precision are constantly being sought in neuroscience. Ultrasound is a promising neuromodulation modality due to its non-invasive potential. However, conventional piezo-based ultrasound neuromodulation using a transducer usually have a spatial resolution of more than a few millimeters, limiting research on specific brain area or neural circuits. Here, a spatially confined optoacoustic emitter is developed for high-precision neuromodulation, allowing neurons to be activated at submillimeter spatial precision. By designing a candle soot-PDMS layered optoacoustic fiber tip (CPOF) with a diameter of 350 μm, we demonstrate the generation of local ultrasound waves with a peak frequency of 3.5 MHz. The ultrasound generated by CPOF can directly activate cortical neurons in culture within a radius of 450 μm around the fiber tip, generating intracellular calcium transients. The CPOF promises to be a novel technique for high-precision neural stimulation and for investigating the mechanism of neurostimulation.