Exploration of genetically encoded voltage indicators based on a chimeric voltage sensing domain

Area of Science:

• Neuroscience
• Molecular Biology
• Biophysics

Background:

• Understanding brain cognitive function requires monitoring large-scale neural activity.
• Genetically encoded voltage indicators (GEVIs) offer potential for optical imaging of neuronal electrical activity.
• Existing GEVIs include voltage-sensitive fluorescent proteins (VSFPs) and microbial opsins.

Purpose of the Study:

• To develop novel GEVIs with improved performance for neural activity monitoring.
• To combine chimeric voltage-sensing domains (VSDs) with the VSFP-Butterfly structure.
• To assess the capability of these new GEVIs in reporting neural activity.

Main Methods:

• Construction of new VSFP designs integrating chimeric VSDs with Butterfly structures.
• Testing GEVIs in cultured cells to measure membrane voltage oscillations.
• In vivo imaging of sensory-evoked cortical population responses in living mice.

Main Results:

• The developed chimeric VSFP-Butterflies successfully reported membrane voltage oscillations up to 200 Hz in cultured cells.
• These novel GEVIs detected sensory-evoked cortical population responses in live mice.
• The new GEVIs demonstrate suitability for imaging brain rhythms in behaving mammals.

Conclusions:

• Chimeric VSFP-Butterflies represent a promising class of GEVIs for neuroscience research.
• These indicators facilitate high-speed optical imaging of neural activity.
• The technology may enable deeper understanding of cognitive functions and brain dynamics.