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

Area of Science:

• Neuroscience
• Bioengineering
• Microscopy

Background:

• Coordinated neural activity across distributed brain regions is crucial for complex behaviors.
• Current miniaturized microscopes have limited fields of view, hindering multi-region recordings.
• Recording neural activity in freely behaving animals is essential for understanding natural behaviors.

Purpose of the Study:

• To develop a novel miniaturized microscope capable of wide-field neural recordings across multiple brain regions.
• To enable cellular-resolution in vivo calcium imaging in distributed neuronal populations.
• To overcome the limitations of current imaging systems for studying brain-wide circuit dynamics.

Main Methods:

• Development of a miniaturized micro-camera array microscope (mini-MCAM) with four fluorescence imaging cameras.
• Each camera captures neural activity across a 4.5 mm × 2.55 mm field of view.
• Imaging of sparsely expressed GCaMP6s neurons across approximately 30 mm² of dorsal cortex.

Main Results:

• The mini-MCAM successfully imaged neural activity across dorsal cortical regions, including motor, somatosensory, visual, retrosplenial, and association cortices.
• Demonstrated cortex-wide, cellular-resolution in vivo calcium (Ca2+) imaging.
• Achieved simultaneous recordings from distributed neuronal populations in both head-fixed and freely behaving mice.

Conclusions:

• The mini-MCAM significantly advances the capability to study brain-wide neural circuit dynamics.
• This technology facilitates research into the neural basis of complex behaviors by enabling large-scale neural recordings.
• The mini-MCAM offers a powerful tool for neuroscience research, particularly in freely moving subjects.