Xuandi Hou, Zhihai Qiu, Quanxiang Xian, Shashwati Kala, Jianing Jing, Kin Fung Wong, Jiejun Zhu, Jinghui Guo, Ting Zhu, Minyi Yang, Lei Sun

Sep 21, 2021
Advanced science
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This study utilizes ultrasound‐responsive nanoscale gas vesicles (GVs) to mediate controllable transcranial ultrasound stimulation. Sonicated neurons and mouse brain display reversible and repeatable Ca2+ responses, and increased c‐Fos expression in the presence of GVs. Mechanosensitive ion channels are found to be involved in mediating the stimulation. This strategy enables targeted stimulation in a deep brain region with high spatiotemporal resolution. Ultrasound is a promising new modality for non‐invasive neuromodulation. Applied transcranially, it can be focused down to the millimeter or centimeter range. The ability to improve the treatment"s spatial resolution to a targeted brain region could help to improve its effectiveness, depending upon the application. The present paper details a neurostimulation scheme using gas‐filled nanostructures, gas vesicles (GVs), as actuators for improving the efficacy and precision of ultrasound stimuli. Sonicated primary neurons display dose‐dependent, repeatable Ca2+ responses, closely synced to stimuli, and increased nuclear expression of the activation marker c‐Fos in the presence of GVs. GV‐mediated ultrasound triggered rapid and reversible Ca2+ responses in vivo and could selectively evoke neuronal activation in a deep‐seated brain region. Further investigation indicate that mechanosensitive ion channels are important mediators of this effect. GVs themselves and the treatment scheme are also found not to induce significant cytotoxicity, apoptosis, or membrane poration in treated cells. Altogether, this study demonstrates a simple and effective method to achieve enhanced and better‐targeted neurostimulation with non‐invasive low‐intensity ultrasound.

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