Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation.
Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation.
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声热遗传学用于非侵入性和细胞型特定的脑深部神经调节。
DOI：
10.1016/j.brs.2021.04.021
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发表时间：
2021-07
影响因子：
7.7
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Yang Y;Pacia CP;Ye D;Zhu L;Baek H;Yue Y;Yuan J;Miller MJ;Cui J;Culver JP;Bruchas MR;Chen H
我们无法以非侵入性方式选择性靶向脑深部神经元，这阻碍了脑功能研究和脑疾病治疗的关键进展。本研究旨在通过将热敏离子通道TRPV1与聚焦超声（FUS）诱导的短暂、无毒的热效应相结合，开发用于非侵入性、深穿透性和细胞类型特异性神经调节的声热遗传学。体外检测TRPV1对FUS超声的敏感性。随后通过双光子显微镜钙成像在小鼠脑中激活遗传定义的神经元中对声热发生学的成功率进行了体内评估。在自由活动的小鼠中记录由声生热刺激引起的脑深部靶点的行为反应。进行离体脑切片的免疫组织化学染色以评价FUS超声处理的安全性。TRPV1被发现是一个超声波敏感的离子通道。在小鼠脑中的FUS超声处理在体内选择性地激活经遗传修饰以表达TRPV 1的神经元。TRPV1表达神经元的时间精确激活实现了其成功率与通过体内磁共振温度测定法测量的FUS靶向脑区域内的峰值温度线性相关。FUS刺激TRPV1表达神经元在纹状体反复诱发运动行为在自由活动的小鼠。基于对神经元完整性、炎症和凋亡标志物的检查，证实FUS超声处理是安全的。这种非侵入性和细胞类型特异性的神经调节方法具有靶向脑深部的能力，有望推进对完整神经系统的研究，并发现治疗神经系统疾病的新方法。
Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain. This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and cell-type-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect. The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of the success rate of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon microscopic calcium imaging. Behavioral response evoked by sonothermogenetic stimulation at a deep brain target was recorded in freely moving mice. Immunohistochemistry staining of ex vivo brain slices was performed to evaluate the safety of FUS sonication. TRPV1 was found to be an ultrasound-sensitive ion channel. FUS sonication at the mouse brain in vivo selectively activated neurons that were genetically modified to express TRPV1. Temporally precise activation of TRPV1-expressing neurons was achieved with its success rate linearly correlated with the peak temperature within the FUS-targeted brain region as measured by in vivo magnetic resonance thermometry. FUS stimulation of TRPV1-expressing neurons at the striatum repeatedly evoked locomotor behavior in freely moving mice. FUS sonication was confirmed to be safe based on inspection of neuronal integrity, inflammation, and apoptosis markers. This noninvasive and cell-type-specific neuromodulation approach with the capability to target the deep brain has the promise to advance the study of the intact nervous system and uncover new ways to treat neurological disorders.
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影响因子：
14.8
作者：
Holtmaat, Anthony;Bonhoeffer, Tobias;Chow, David K.;Chuckowree, Jyoti;De Paola, Vincenzo;Hofer, Sonja B.;Huebener, Mark;Keck, Tara;Knott, Graham;Lee, Wei-Chung A.;Mostany, Ricardo;Mrsic-Flogel, Tom D.;Nedivi, Elly;Portera-Cailliau, Carlos;Svoboda, Karel;Trachtenberg, Joshua T.;Wilbrecht, Linda
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Wilbrecht, Linda
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影响因子：
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作者：
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影响因子：
46.9
作者：
Chen R;Gore F;Nguyen QA;Ramakrishnan C;Patel S;Kim SH;Raffiee M;Kim YS;Hsueh B;Krook-Magnusson E;Soltesz I;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
3.7
作者：
Kim JH;Lee SR;Li LH;Park HJ;Park JH;Lee KY;Kim MK;Shin BA;Choi SY
通讯作者：
Choi SY
影响因子：
158.5
作者：
Follett, Kenneth A.;Weaver, Frances M.;Reda, Domenic J.
通讯作者：
Reda, Domenic J.