Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification
Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification
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聚焦超声通过机械敏感的钙积累和离子通道放大来刺激神经元
DOI：
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Mikhail G. Shapiro
中科院分区：
文献类型：
--
作者：
Sangjin Yoo;D. Mittelstein;Robert C. Hurt;Jérôme J. Lacroix;Mikhail G. Shapiro
超声神经调节具有独特的潜力，可以在不需要化学或遗传修饰的情况下，以高空间精度提供对大脑深层区域神经活动的非侵入性控制。然而，聚焦超声刺激哺乳动物神经元的生物分子和细胞机制尚不清楚，这给这项技术在研究和潜在的临床应用中的应用带来了巨大的挑战。在这里，我们展示了聚焦超声通过一种主要的机械机制来兴奋神经元，这种机制是由特定的钙选择性机械敏感离子通道介导的。这些通道的激活导致钙离子逐渐积聚，钙离子和电压门控通道放大，产生爆发式放电反应。这种兴奋的发生不需要空化、温度变化、大规模变形和突触传递。特定离子通道的药物和遗传抑制会导致对超声波的反应减弱，而过度表达这些通道会导致更强的超声波刺激。这些发现为超声波对神经元的影响提供了一个关键的缺失解释，并促进了超声波神经调节和声遗传学作为神经科学研究的独特工具的进一步发展。
Ultrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, the biomolecular and cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for the use of this technology in research and potential clinical applications. Here, we show that focused ultrasound excites neurons through a primarily mechanical mechanism mediated by specific calcium-selective mechanosensitive ion channels. The activation of these channels results in a gradual build-up of calcium, which is amplified by calcium- and voltage-gated channels, generating a burst firing response. Cavitation, temperature changes, large-scale deformation, and synaptic transmission are not required for this excitation to occur. Pharmacological and genetic inhibition of specific ion channels leads to reduced responses to ultrasound, while over-expressing these channels results in stronger ultrasonic stimulation. These findings provide a critical missing explanation for the effect of ultrasound on neurons and facilitate the further development of ultrasonic neuromodulation and sonogenetics as unique tools for neuroscience research.
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影响因子：
2.9
作者：
Kim, Hyungmin;Taghados, Seyed Javid;Fischer, Krisztina;Maeng, Lee-So;Park, Shinsuk;Yoo, Seung-Schik
通讯作者：
Yoo, Seung-Schik
影响因子：
3.9
作者：
Niu, Xiaodan;Yu, Kai;He, Bin
通讯作者：
He, Bin
影响因子：
2.9
作者：
Ye PP;Brown JR;Pauly KB
通讯作者：
Pauly KB
DOI：
10.1146/annurev-chembioeng-060817-084034
发表时间：
2018-06-07
影响因子：
8.4
作者：
Maresca D;Lakshmanan A;Abedi M;Bar-Zion A;Farhadi A;Lu GJ;Szablowski JO;Wu D;Yoo S;Shapiro MG
通讯作者：
Shapiro MG
影响因子：
13.6
作者：
Gigliotti, Joseph C.;Huang, Liping;Okusa, Mark D.
通讯作者：
Okusa, Mark D.