Pan-cortical cellular imaging in freely behaving mice using a miniaturized micro-camera array microscope (mini-MCAM).

Area of Science:

• Neuroscience
• Bioimaging
• Cerebral Cortex Research

Background:

• Understanding complex behaviors requires simultaneous neural activity recording from distributed brain circuits in freely moving animals.
• Existing miniaturized microscopes have limited fields of view, hindering multi-region neural activity measurements.

Purpose of the Study:

• To introduce a novel miniaturized micro-camera array microscope (mini-MCAM) for broad-area neural recording.
• To enable simultaneous, cortex-wide, cellular-resolution in vivo calcium imaging in mice.

Main Methods:

• Development of the miniaturized micro-camera array microscope (mini-MCAM) with four fluorescence imaging micro-cameras.
• Each camera captures neural activity across a 4.5 mm x 2.55 mm field of view.
• Demonstration of in vivo calcium (Ca2+) imaging in both head-fixed and freely behaving mice.

Main Results:

• The mini-MCAM cumulatively images over 30 mm² of the dorsal cortex.
• It captures neural activity from sparsely expressed GCaMP6s neurons across motor, somatosensory, visual, retrosplenial, and association cortices.
• Achieved cortex-wide cellular resolution in vivo calcium imaging.

Conclusions:

• The mini-MCAM overcomes FOV limitations of current microscopes for large-scale neural recording.
• This technology facilitates studying brain circuit coordination underlying complex behaviors in behaving animals.
• Enables unprecedented insights into cortex-wide neural dynamics.