Imaging neural circuit dynamics with a voltage-sensitive fluorescent protein

Area of Science:

• Neuroscience
• Molecular Biology
• Biophysics

Background:

• Neuronal population activity is crucial for understanding brain function during behavior.
• Current methods like EEG, LFP, and voltage-sensitive dyes have limitations in cell-type specificity.
• Genetically encoded voltage indicators offer a promising approach for targeted neuronal signal detection.

Purpose of the Study:

• To introduce and characterize Butterfly, a novel voltage-sensitive fluorescent protein (VSFP) for advanced voltage imaging.
• To demonstrate the utility of VSFP-Butterfly for detecting neuronal activity across different scales, from single neurons to brain activity in vivo.
• To provide a new genetic tool for cell class-specific voltage imaging and studying neuronal population dynamics.

Main Methods:

• Development and characterization of a new voltage-sensitive fluorescent protein (VSFP-Butterfly).
• Assessment of membrane targeting, response gain, kinetics, and signal-to-noise ratio of VSFP-Butterfly.
• In vitro and in vivo experiments to validate VSFP-Butterfly's ability to report neuronal activity, including synaptic potentials and network oscillations.

Main Results:

• VSFP-Butterfly exhibits reliable membrane targeting and optimal response gain near neuronal resting membrane potential.
• The protein demonstrates fast kinetics suitable for capturing single-cell synaptic responses and a high signal-to-noise ratio.
• Butterfly successfully imaged excitatory postsynaptic potentials (EPSPs), whisker-evoked responses, gamma oscillations, and slow brain waves in vivo.

Conclusions:

• VSFP-Butterfly is a practical tool for cell class-specific voltage imaging.
• This genetically encoded voltage indicator expands the toolkit for detecting neuronal population dynamics.
• The findings pave the way for more precise investigations into neural circuit function.