High‐Precision Photoacoustic Neural Modulation Uses a Non‐Thermal Mechanism

Abstract Neuromodulation is a powerful tool for fundamental studies in neuroscience and potential treatments of neurological disorders. Both photoacoustic (PA) and photothermal (PT) effects are harnessed for non‐genetic high‐precision neural stimulation. Using a fiber‐based device excitable by a nanosecond pulsed laser and a continuous wave laser for PA and PT stimulation, respectively, PA and PT neuromodulation is systematically investigated at the single neuron level. These results show that to achieve the same level of neuron activation recorded by Ca 2+ imaging, the laser energy needed for PA stimulation is 1/40 of that needed for PT stimulation. The threshold energy for PA stimulation is found to be further reduced in neurons overexpressing mechano‐sensitive channels, indicating direct involvement of mechano‐sensitive channels in PA stimulation. Electrophysiology study of single neurons upon PA and PT stimulation is performed by patch clamp recordings. Electrophysiological features induced by PA are distinct from those by PT, confirming that PA and PT stimulation operate through different mechanisms. These insights offer a foundation for the rational design of more efficient and safer non‐genetic neural modulation approaches.