2021
DOI: 10.1016/j.brs.2021.04.021
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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 celltype-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 e… Show more

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Cited by 63 publications
(65 citation statements)
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“…We performed a comparative analysis of FUSIN, DI, FUS-BBBD, and IN delivery of AAV5-hSyn-EGFP. The AAV dose used in DI was limited by the injection volume (1.2 µL), 26 , 27 and the injection was targeted at the mouse cortex. The AAV dose for all other methods was 24 μL.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…We performed a comparative analysis of FUSIN, DI, FUS-BBBD, and IN delivery of AAV5-hSyn-EGFP. The AAV dose used in DI was limited by the injection volume (1.2 µL), 26 , 27 and the injection was targeted at the mouse cortex. The AAV dose for all other methods was 24 μL.…”
Section: Resultsmentioning
confidence: 99%
“…Each mouse in the DI group was injected with 1.2 μL of AAVs following the established protocol. 26 , 27 …”
Section: Methodsmentioning
confidence: 99%
“…Despite its scalability, ATAC has limited temporal control over the stimulation duration, which depends on the circulation time of CNO. Ultrasound has also been used as a thermal stimulus following direct injection of lentivirus-encoded thermally-sensitive TRPV1 ion channels in sonothermogenetics [34]. Sonothermogenetic activation evoked locomotor behavior in freely moving mice, only when local temperature during high-duty-cycle sonication exceeded 42 C. However, this approach required either anesthesia or implantation of a construct bearing the FUS transducer onto the mouse skull, hindering application in larger species or humans.…”
Section: Discussionmentioning
confidence: 99%
“…It can non-invasively penetrate through the skull bone and focus on targeted brain locations with millimeter precision. tFUS at low intensity levels has been used for neuromodulation by targeting different parts of the brain ( Legon et al, 2014 ; Ibsen et al, 2015 ; Qiu et al, 2020 ; Yang et al, 2021 ; Darmani et al, 2022 ). tFUS combined with microbubbles can non-invasively, locally, and reversibly disrupt the blood-brain barrier for brain drug delivery ( Chen and Konofagou, 2014 ; Lipsman et al, 2018 ; Chen et al, 2021 ; Hu et al, 2022a ) or brain tumor-derived molecular biomarker release ( Zhu et al, 2018 ; Meng et al, 2021 ; Pacia et al, 2022 ).…”
Section: Introductionmentioning
confidence: 99%