Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy
Abstract Widefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the limited performance of current GEVIs restricts their deployment for single-trial imaging of rapi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41975-3 |
| _version_ | 1827709494624256000 |
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| author | Xiaoyu Lu Yunmiao Wang Zhuohe Liu Yueyang Gou Dieter Jaeger François St-Pierre |
| author_facet | Xiaoyu Lu Yunmiao Wang Zhuohe Liu Yueyang Gou Dieter Jaeger François St-Pierre |
| author_sort | Xiaoyu Lu |
| collection | DOAJ |
| description | Abstract Widefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the limited performance of current GEVIs restricts their deployment for single-trial imaging of rapid neuronal voltage dynamics. Here, we developed a high-throughput platform to screen for GEVIs that combine fast kinetics with high brightness, sensitivity, and photostability under widefield one-photon illumination. Rounds of directed evolution produced JEDI-1P, a green-emitting fluorescent indicator with enhanced performance across all metrics. Next, we optimized a neonatal intracerebroventricular delivery method to achieve cost-effective and wide-spread JEDI-1P expression in mice. We also developed an approach to correct optical measurements from hemodynamic and motion artifacts effectively. Finally, we achieved stable brain-wide voltage imaging and successfully tracked gamma-frequency whisker and visual stimulations in awake mice in single trials, opening the door to investigating the role of high-frequency signals in brain computations. |
| first_indexed | 2024-03-10T17:22:46Z |
| format | Article |
| id | doaj.art-c1aeaafd7f194a15b4104d77223a88d9 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:46Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c1aeaafd7f194a15b4104d77223a88d92023-11-20T10:17:44ZengNature PortfolioNature Communications2041-17232023-10-0114112210.1038/s41467-023-41975-3Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopyXiaoyu Lu0Yunmiao Wang1Zhuohe Liu2Yueyang Gou3Dieter Jaeger4François St-Pierre5Systems, Synthetic, and Physical Biology Program, Rice UniversityNeuroscience Graduate Program, Emory UniversityDepartment of Electrical and Computer Engineering, Rice UniversityDepartment of Neuroscience, Baylor College of MedicineBiology Department, Emory UniversitySystems, Synthetic, and Physical Biology Program, Rice UniversityAbstract Widefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the limited performance of current GEVIs restricts their deployment for single-trial imaging of rapid neuronal voltage dynamics. Here, we developed a high-throughput platform to screen for GEVIs that combine fast kinetics with high brightness, sensitivity, and photostability under widefield one-photon illumination. Rounds of directed evolution produced JEDI-1P, a green-emitting fluorescent indicator with enhanced performance across all metrics. Next, we optimized a neonatal intracerebroventricular delivery method to achieve cost-effective and wide-spread JEDI-1P expression in mice. We also developed an approach to correct optical measurements from hemodynamic and motion artifacts effectively. Finally, we achieved stable brain-wide voltage imaging and successfully tracked gamma-frequency whisker and visual stimulations in awake mice in single trials, opening the door to investigating the role of high-frequency signals in brain computations.https://doi.org/10.1038/s41467-023-41975-3 |
| spellingShingle | Xiaoyu Lu Yunmiao Wang Zhuohe Liu Yueyang Gou Dieter Jaeger François St-Pierre Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy Nature Communications |
| title | Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy |
| title_full | Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy |
| title_fullStr | Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy |
| title_full_unstemmed | Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy |
| title_short | Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy |
| title_sort | widefield imaging of rapid pan cortical voltage dynamics with an indicator evolved for one photon microscopy |
| url | https://doi.org/10.1038/s41467-023-41975-3 |
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