Abstract
Neuromodulation at high spatial resolution poses great significance in advancing fundamental knowledge in the field of neuroscience and offering novel clinical treatments. Here, we developed a tapered fiber optoacoustic emitter (TFOE) generating an ultrasound field with a high spatial precision of 39.6 µm, enabling optoacoustic activation of single neurons or subcellular structures, such as axons and dendrites. Temporally, a single acoustic pulse of sub-microsecond converted by the TFOE from a single laser pulse of 3 ns is shown as the shortest acoustic stimuli so far for successful neuron activation. The precise ultrasound generated by the TFOE enabled the integration of the optoacoustic stimulation with highly stable patch-clamp recording on single neurons. Direct measurements of the electrical response of single neurons to acoustic stimulation, which is difficult for conventional ultrasound stimulation, have been demonstrated. By coupling TFOE with ex vivo brain slice electrophysiology, we unveil cell-type-specific responses 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 ultrasound neurostimulation.
Highlights
Neuromodulation at high spatial precision poses great significance in advancing fundamental knowledge in the field of neuroscience, as the firing of a small population or even single neurons can alter animal behavior or brain state[1,2]
To increase optoacoustic conversion efficiency in the tapered fiber and assure minimum light leakage, the optoacoustic carbon nanotubes (CNT)/PDMS coating was prepared with a large CNT concentration of 15%, by introducing isopropyl alcohol (IPA) to form IPA-coated CNTs with hydroxyl groups
The acoustic wave generated by tapered fiber optoacoustic emitter (TFOE) allows optoacoustic stimulation along with simultaneous monitoring of cell responses using whole-cell patch-clamp recording, which has been reported to be challenging under conventional ultrasound stimulation
Summary
Neuromodulation at high spatial precision poses great significance in advancing fundamental knowledge in the field of neuroscience, as the firing of a small population or even single neurons can alter animal behavior or brain state[1,2]. As the most prescribed neuromodulation method clinically, has been used for treating neurological and Toward non-genetic stimulation, photothermal neural stimulations based on light absorption of water have been reported[12,13,14], and it has attracted increasing interest in basic science and translational application[15,16]. In infrared photothermal neural stimulation (INS), near-infrared light between 1.5 and 2 μm in wavelength is delivered through a fiber and converted into temperature increase in water with sub-millimeter precision[15,17], where the associated heating raises a significant concern of tissue damage[18]. As a rapidly growing modality, focused ultrasound has been harnessed in a myriad of brain neuromodulation applications[19,20,21], given
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