  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.
