Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice

Xuandi Hou, Jianing Jing, Yizhou Jiang, Xiaohui Huang, Quanxiang Xian, Ting Lei, Jiejun Zhu, Kin Fung Wong, Xinyi Zhao, Min Su, Danni Li, Langzhou Liu, Zhihai Qiu and Lei Sun ()
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Xuandi Hou: The Hong Kong Polytechnic University
Jianing Jing: The Hong Kong Polytechnic University
Yizhou Jiang: The Hong Kong Polytechnic University
Xiaohui Huang: The Hong Kong Polytechnic University
Quanxiang Xian: The Hong Kong Polytechnic University
Ting Lei: The Hong Kong Polytechnic University
Jiejun Zhu: The Hong Kong Polytechnic University
Kin Fung Wong: The Hong Kong Polytechnic University
Xinyi Zhao: The Hong Kong Polytechnic University
Min Su: The Hong Kong Polytechnic University
Danni Li: The Hong Kong Polytechnic University
Langzhou Liu: The Hong Kong Polytechnic University
Zhihai Qiu: Hengqin
Lei Sun: The Hong Kong Polytechnic University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Ultrasound is an acoustic wave which can noninvasively penetrate the skull to deep brain regions, enabling neuromodulation. However, conventional ultrasound’s spatial resolution is diffraction-limited and low-precision. Here, we report acoustic nanobubble-mediated ultrasound stimulation capable of localizing ultrasound’s effects to only the desired brain region in male mice. By varying the delivery site of nanobubbles, ultrasound could activate specific regions of the mouse motor cortex, evoking EMG signaling and limb movement, and could also, separately, activate one of two nearby deep brain regions to elicit distinct behaviors (freezing or rotation). Sonicated neurons displayed reversible, low-latency calcium responses and increased c-Fos expression in the sub-millimeter-scale region with nanobubbles present. Ultrasound stimulation of the relevant region also modified depression-like behavior in a mouse model. We also provide evidence of a role for mechanosensitive ion channels. Altogether, our treatment scheme allows spatially-targetable, repeatable and temporally-precise activation of deep brain circuits for neuromodulation without needing genetic modification.

Date: 2024
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DOI: 10.1038/s41467-024-46461-y

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