Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice

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 cap...

Full description

Bibliographic Details
Main Authors: 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, Lei Sun
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-46461-y
_version_ 1797259174621478912
author 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
Lei Sun
author_facet 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
Lei Sun
author_sort Xuandi Hou
collection DOAJ
description 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.
first_indexed 2024-04-24T23:05:14Z
format Article
id doaj.art-bd8873157a9743d2b422bb48371f4024
institution Directory Open Access Journal
issn 2041-1723
language English
last_indexed 2024-04-24T23:05:14Z
publishDate 2024-03-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj.art-bd8873157a9743d2b422bb48371f40242024-03-17T12:31:57ZengNature PortfolioNature Communications2041-17232024-03-0115111810.1038/s41467-024-46461-yNanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in miceXuandi Hou0Jianing Jing1Yizhou Jiang2Xiaohui Huang3Quanxiang Xian4Ting Lei5Jiejun Zhu6Kin Fung Wong7Xinyi Zhao8Min Su9Danni Li10Langzhou Liu11Zhihai Qiu12Lei Sun13Department of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityGuangdong Institute of Intelligence Science and Technology, HengqinDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityAbstract 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.https://doi.org/10.1038/s41467-024-46461-y
spellingShingle 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
Lei Sun
Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
Nature Communications
title Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
title_full Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
title_fullStr Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
title_full_unstemmed Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
title_short Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
title_sort nanobubble actuated ultrasound neuromodulation for selectively shaping behavior in mice
url https://doi.org/10.1038/s41467-024-46461-y
work_keys_str_mv AT xuandihou nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT jianingjing nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT yizhoujiang nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT xiaohuihuang nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT quanxiangxian nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT tinglei nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT jiejunzhu nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT kinfungwong nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT xinyizhao nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT minsu nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT dannili nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT langzhouliu nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT zhihaiqiu nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice
AT leisun nanobubbleactuatedultrasoundneuromodulationforselectivelyshapingbehaviorinmice