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A positively tuned voltage indicator for extended electrical recordings in the brain
S Wenceslao Evans1, Dong-Qing Shi2, Mariya Chavarha3
1Department of Neurobiology, Stanford University Medical Center, Stanford, CA, USA.
Nature Methods
|July 10, 2023
Summary
New genetically encoded voltage indicators (GEVIs) offer enhanced photostability for prolonged optical recording of brain electrical signals. These improved GEVI tools enable clearer, longer voltage imaging in neuroscience research.
Area of Science:
- Neuroscience
- Biotechnology
- Optical Imaging
Background:
- Genetically encoded voltage indicators (GEVIs) allow optical recording of neural electrical activity.
- Existing GEVIs have limitations in photostability for prolonged imaging.
- Calcium indicators lack the temporal resolution for precise electrical signal capture.
Purpose of the Study:
- To engineer enhanced GEVIs with improved photostability for extended voltage imaging.
- To demonstrate the utility of novel GEVIs in standard one- and two-photon microscopy.
- To compare the performance of new GEVIs against existing voltage and calcium indicators.
Main Methods:
- Engineering of ASAP family GEVIs with inverted fluorescence-voltage relationship.
- Testing GEVIs in standard one- and two-photon microscopy setups.
- Simultaneous voltage and calcium imaging in biological samples.
Main Results:
- Developed ASAP4b and ASAP4e GEVIs with significantly increased fluorescence upon depolarization.
- Achieved single-trial spike detection in mice using ASAP4e over minutes.
- Demonstrated successful performance of ASAP4b and ASAP4e under both one- and two-photon illumination.
- Showcased superior temporal resolution for spike detection compared to calcium indicators.
Conclusions:
- ASAP4b and ASAP4e GEVIs enhance photostability, enabling longer duration voltage recordings.
- These novel GEVIs are compatible with standard one- and two-photon microscopes.
- The improved GEVIs offer advanced capabilities for neuroscience research, including precise electrical signal monitoring.
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