@article{6254658bbf044d559323424c09189860,
title = "Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation",
abstract = "Background: 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. Objective: 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. Methods: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon 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. Results: 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. Conclusions: This noninvasive and cell-type-specific neuromodulation approach with the capability to stimulate deep brain has the promise to advance the study of the intact nervous system and uncover new ways to treat neurological disorders.",
keywords = "Calcium imaging, Focused ultrasound, Ion channel, Neuromodulation, Sonothermogenetics",
author = "Yaoheng Yang and Pacia, {Christopher Pham} and Dezhuang Ye and Lifei Zhu and Hongchae Baek and Yimei Yue and Jinyun Yuan and Miller, {Mark J.} and Jianmin Cui and Culver, {Joseph P.} and Bruchas, {Michael R.} and Hong Chen",
note = "Funding Information: This work was supported by the National Institutes of Health (NIH) BRAIN Initiative ( R01MH116981 ) and NIBIB ( R01EB027223 and R01EB030102 ). This work was supported by the Hope Center Viral Vectors Core at Washington University School of Medicine . The studies presented in this work were carried out, in part, using the Small Animal MR Facility of the Mallinckrodt Institute of Radiology, Washington University. We thank Dr. Hunter Banks, Dr. Lu Zhao, and Ms. Lindsey Brier for the insightful discussions. We thank D. Mingjie Li from the Hope Center Viral Vectors Core at Washington University for preparing the lentiviral and AAV vectors. We appreciate the help of Dr. James D. Quirk in thermometry mapping using magnetic resonance imaging. We thank Dr. Meaghan Creed for helping with viral injection. We also thank Dr. Si Chen for helping with immunofluorescence staining of in-vitro cells. Funding Information: This work was supported by the National Institutes of Health (NIH) BRAIN Initiative (R01MH116981) and NIBIB (R01EB027223 and R01EB030102). This work was supported by the Hope Center Viral Vectors Core at Washington University School of Medicine. The studies presented in this work were carried out, in part, using the Small Animal MR Facility of the Mallinckrodt Institute of Radiology, Washington University. We thank Dr. Hunter Banks, Dr. Lu Zhao, and Ms. Lindsey Brier for the insightful discussions. We thank D. Mingjie Li from the Hope Center Viral Vectors Core at Washington University for preparing the lentiviral and AAV vectors. We appreciate the help of Dr. James D. Quirk in thermometry mapping using magnetic resonance imaging. We thank Dr. Meaghan Creed for helping with viral injection. We also thank Dr. Si Chen for helping with immunofluorescence staining of in-vitro cells. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jul,
day = "1",
doi = "10.1016/j.brs.2021.04.021",
language = "English",
volume = "14",
pages = "790--800",
journal = "Brain Stimulation",
issn = "1935-861X",
number = "4",
}