Miniaturized head-mounted microscope for whole-cortex mesoscale imaging in freely behaving mice

Area of Science:

• Neuroscience
• Bioengineering
• Optical Imaging

Background:

• Mesoscale cortical activity imaging in mice is typically limited to head-fixed preparations.
• Neural activity during unrestrained behavior differs significantly from head-fixed conditions.
• Whole-cortex imaging in freely behaving mice is crucial for understanding natural neural dynamics.

Purpose of the Study:

• To develop a miniaturized, head-mounted microscope for whole-cortex imaging in freely behaving mice.
• To enable mesoscale calcium activity recording across the dorsal cortex during natural behaviors.
• To overcome limitations of head-fixed preparations in neuroscience research.

Main Methods:

• Introduction of the 'mini-mScope', a widefield, head-mounted fluorescence microscope.
• Compatibility with transparent polymer skull preparations for chronic imaging.
• Utilizing genetically encoded calcium indicators for neural activity visualization.

Main Results:

• The mini-mScope provides a wide field of view (8x10 mm²) and high resolution (39-56 µm).
• It weighs less than 4g, allowing for minimal impact on animal behavior.
• Successful recording of mesoscale calcium activity during various behaviors and physiological states.

Conclusions:

• The mini-mScope facilitates whole-cortex neural activity imaging in freely behaving mice.
• This technology bridges the gap between head-fixed and naturalistic behavioral studies.
• It offers a powerful tool for investigating brain-wide neural dynamics during complex behaviors.