Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation
Brain stimulation with ultra-low-intensity ultrasound has rarely been investigated due to the lack of a reliable device to measure small neuronal signal changes made by the ultra-low intensity range. We propose Ultrasonocoverslip, an ultrasound-transducer-integrated-glass-coverslip that determines t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X23018740 |
| _version_ | 1797644768555040768 |
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| author | Keunhyung Lee Jung Moo Lee Tien Thuy Phan C. Justin Lee Joo Min Park Jinhyoung Park |
| author_facet | Keunhyung Lee Jung Moo Lee Tien Thuy Phan C. Justin Lee Joo Min Park Jinhyoung Park |
| author_sort | Keunhyung Lee |
| collection | DOAJ |
| description | Brain stimulation with ultra-low-intensity ultrasound has rarely been investigated due to the lack of a reliable device to measure small neuronal signal changes made by the ultra-low intensity range. We propose Ultrasonocoverslip, an ultrasound-transducer-integrated-glass-coverslip that determines the minimum intensity for brain cell activation. Brain cells can be cultured directly on Ultrasonocoverslip to simultaneously deliver uniform ultrasonic pressure to hundreds of cells with real-time monitoring of cellular responses using fluorescence microscopy and single-cell electrophysiology. The sensitivity for detecting small responses to ultra-low-intensity ultrasound can be improved by averaging simultaneously obtained responses. Acoustic absorbers can be placed under Ultrasonocoverslip, and stimuli distortions are substantially reduced to precisely deliver user-intended acoustic stimulations. With the proposed device, we discover the lowest acoustic threshold to induce reliable neuronal excitation releasing glutamate. Furthermore, mechanistic studies on the device show that the ultra-low-intensity ultrasound stimulation induces cell type-specific neuromodulation by activating astrocyte-mediated neuronal excitation without direct neuronal involvement. The performance of ultra-low-intensity stimulation is validated by in vivo experiments demonstrating improved safety and specificity in motor modulation of tail movement compared to that with supra-watt-intensity. |
| first_indexed | 2024-03-11T14:35:49Z |
| format | Article |
| id | doaj.art-9b743c474bdb499ebfc4f2d8f7de7b19 |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-03-11T14:35:49Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-9b743c474bdb499ebfc4f2d8f7de7b192023-10-31T04:08:58ZengElsevierBrain Stimulation1935-861X2023-09-0116515331548Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulationKeunhyung Lee0Jung Moo Lee1Tien Thuy Phan2C. Justin Lee3Joo Min Park4Jinhyoung Park5Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Republic of KoreaCenter for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of KoreaIBS School, University of Science and Technology (UST), Daejeon, Republic of KoreaCenter for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of KoreaCenter for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea; IBS School, University of Science and Technology (UST), Daejeon, Republic of Korea; Corresponding author. Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea.Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Republic of Korea; Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea; Corresponding author. Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Republic of Korea.Brain stimulation with ultra-low-intensity ultrasound has rarely been investigated due to the lack of a reliable device to measure small neuronal signal changes made by the ultra-low intensity range. We propose Ultrasonocoverslip, an ultrasound-transducer-integrated-glass-coverslip that determines the minimum intensity for brain cell activation. Brain cells can be cultured directly on Ultrasonocoverslip to simultaneously deliver uniform ultrasonic pressure to hundreds of cells with real-time monitoring of cellular responses using fluorescence microscopy and single-cell electrophysiology. The sensitivity for detecting small responses to ultra-low-intensity ultrasound can be improved by averaging simultaneously obtained responses. Acoustic absorbers can be placed under Ultrasonocoverslip, and stimuli distortions are substantially reduced to precisely deliver user-intended acoustic stimulations. With the proposed device, we discover the lowest acoustic threshold to induce reliable neuronal excitation releasing glutamate. Furthermore, mechanistic studies on the device show that the ultra-low-intensity ultrasound stimulation induces cell type-specific neuromodulation by activating astrocyte-mediated neuronal excitation without direct neuronal involvement. The performance of ultra-low-intensity stimulation is validated by in vivo experiments demonstrating improved safety and specificity in motor modulation of tail movement compared to that with supra-watt-intensity.http://www.sciencedirect.com/science/article/pii/S1935861X23018740UltrasonocoverslipUltrasound transducer-integrated glass-coverslipUltra-low-intensity ultrasound stimulationCell type-specific neuromodulationGlutamate-mediated neuronal excitationTRPA1 |
| spellingShingle | Keunhyung Lee Jung Moo Lee Tien Thuy Phan C. Justin Lee Joo Min Park Jinhyoung Park Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation Brain Stimulation Ultrasonocoverslip Ultrasound transducer-integrated glass-coverslip Ultra-low-intensity ultrasound stimulation Cell type-specific neuromodulation Glutamate-mediated neuronal excitation TRPA1 |
| title | Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation |
| title_full | Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation |
| title_fullStr | Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation |
| title_full_unstemmed | Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation |
| title_short | Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation |
| title_sort | ultrasonocoverslip in vitro platform for high throughput assay of cell type specific neuromodulation with ultra low intensity ultrasound stimulation |
| topic | Ultrasonocoverslip Ultrasound transducer-integrated glass-coverslip Ultra-low-intensity ultrasound stimulation Cell type-specific neuromodulation Glutamate-mediated neuronal excitation TRPA1 |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X23018740 |
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