Miniaturized widefield microscope for high speed in vivo voltage imaging

Area of Science:

• Neuroscience
• Biomedical Engineering
• Optical Imaging

Background:

• Functional imaging in freely moving animals using genetically encoded voltage indicators (GEVIs) offers advanced capabilities for neuroscience.
• Studying the behavioral relevance of neural activity requires high spatial and temporal precision.
• Miniaturizing imaging systems for efficient voltage spike detection has been a significant challenge.

Purpose of the Study:

• To develop a miniaturized microscope system for in vivo voltage imaging.
• To overcome challenges in resolving small fluorescence changes from voltage spikes.
• To enable high-speed neural activity recording in freely moving subjects.

Main Methods:

• Designed a miniaturized microscope with a numerical aperture of 0.6, 250 μm field of view, and 1.3 mm working distance.
• The microscope system weighs 16.4 g, facilitating use in freely moving animals.
• Utilized genetically encoded voltage indicators (GEVIs) for fluorescence-based neural activity detection.

Main Results:

• Successfully imaged in vivo voltage spikes from the Voltron2 indicator.
• Achieved a spike peak-to-noise ratio greater than 3.
• Operated the system at a high frame rate of 530 Hz.

Conclusions:

• The developed miniaturized microscope is capable of high-performance voltage imaging in freely moving animals.
• This technology advances the study of neural activity and its relation to behavior.
• The system's specifications enable precise and rapid capture of neural signals.