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As an emerging technology, transcranial focused ultrasound has been demonstrated to successfully evoke motor responses in mice, rabbits, and sensory/motor responses in humans. Yet, the spatial resolution of ultrasound does not allow for high-precision stimulation. Here, we developed a tapered fiber optoacoustic emitter (TFOE) for optoacoustic stimulation of neurons with an unprecedented spatial resolution of 20 microns, enabling selective activation of single neurons or subcellular structures, such as axons and dendrites. A single acoustic pulse of 1 microsecond converted by the TFOE from a single laser pulse of 3 nanoseconds is shown as the shortest acoustic stimuli so far for successful neuron activation. The highly localized ultrasound generated by the TFOE made it possible to integrate the optoacoustic stimulation and highly stable patch clamp recording on single neurons. Direct measurements of electrical response of single neurons to acoustic stimulation, which is difficult for conventional ultrasound stimulation, have been demonstrated for the first time. By coupling TFOE with ex vivo brain slice electrophysiology, we unveil cell-type-specific response of excitatory and inhibitory neurons to acoustic stimulation. These results demonstrate that TFOE is a non-genetic single-cell and sub-cellular modulation technology, which could shed new insights into the mechanism of neurostimulation.
Optoacoustic image formation is conventionally based upon ultrasound time-of-flight readings from multiple detection positions. Herein, we exploit acoustic scattering to physically encode the position of optical absorbers in the acquired signals, thu
A diamond nano-crystal hosting a single nitrogen vacancy (NV) center is optically selected with a confocal scanning microscope and positioned deterministically onto the subwavelength-diameter waist of a tapered optical fiber (TOF) with the help of an
Focused ultrasound has attracted great attention in minimally invasive therapy, gene delivery, brain stimulation, etc. Frequency below 1 MHz has been identified preferable for high-efficacy drug delivery, gene transfection and neurostimulation due to
Deep supervised neural networks trained to classify objects have emerged as popular models of computation in the primate ventral stream. These models represent information with a high-dimensional distributed population code, implying that inferotempo
The cerebrospinal fluid (CSF) constitutes an interface through which chemical cues can reach and modulate the activity of neurons located at the epithelial boundary within the entire nervous system. Here, we investigate the role and functional connec