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

The advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. However, neural activity during unrestrained behavior substantially differs from neural activity in head-fixed animals. For whole-cortex imaging in freely behaving mice, we here present the “mini-mScope,” a wide-field, miniaturized, and head-mounted fluorescence microscope compatible with transparent polymer skull preparations. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the mini-mScope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 μm. We have used the mini-mScope to record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, social interactions, and transitions from wakefulness to sleep.