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Updated: May 19, 2026
09:57
Imaging Membrane Potential with Two Types of Genetically Encoded Fluorescent Voltage Sensors
Published on: February 4, 2016
Improving positively tuned voltage indicators for faster kinetics and higher contrast
Sungmoo Lee1,2,3, Guofeng Zhang1,2,4,3, Yukun Alex Hao1,2
1Department of Neurobiology, Stanford University, Stanford, CA, USA.
Biorxiv : the Preprint Server for Biology
|May 18, 2026
Summary
Researchers developed ASAP6c, a novel voltage indicator that significantly enhances fluorescence signals for detecting neural activity. This advancement offers a 3-fold improvement in signal-to-noise ratio for in vivo imaging.
Area of Science:
- Neuroscience
- Biotechnology
- Molecular Biology
Background:
- Positively tuned ASAP-family voltage indicators like ASAP4e offer superior photostability.
- However, their signal-to-noise ratios for detecting neural spikes are comparable to earlier versions like ASAP3.
- Improving spike detection sensitivity in voltage indicators is crucial for neuroscience research.
Purpose of the Study:
- To enhance the signal-to-noise ratio for spike detection in positively tuned ASAP voltage indicators.
- To develop a faster and more sensitive voltage indicator for in vivo imaging of neural activity.
Main Methods:
- Structure-guided saturation mutagenesis was performed on an ASAP4e predecessor.
- Screening focused on identifying variants with faster response kinetics.
- The performance of the new variant, ASAP6c, was evaluated in vivo using one-photon and two-photon imaging.
Main Results:
- ASAP6c demonstrated approximately 100% increases in fluorescence in response to single action potentials.
- ASAP6c achieved a 3-fold improvement in signal-to-noise ratio compared to ASAP4e.
- The enhanced performance was observed in both one-photon and two-photon imaging modalities in vivo.
Conclusions:
- ASAP6c represents a significant improvement over existing positively tuned ASAP voltage indicators for detecting neural spikes.
- The development of ASAP6c offers a more sensitive tool for in vivo electrophysiology and neuroscience research.
- This work highlights the potential of structure-guided engineering to optimize voltage indicator performance.
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