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 headfixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortical surface during a variety of behaviors. However, neural activity during free, unrestrained behavior significantly differs from that observed in headfixed animals. The ability to perform mesoscale imaging of the cortex in freely behaving mice may launch new avenues of scientific enquiry. Here we present the ‘Mesoscope’, a miniature, head-mountable imaging device compatible with transparent polymer skulls recently developed by our group. With an 8x10 mm field of view, the Mesoscope can image most of the mouse dorsal cortex and weighs only 3.7 grams. Here, we show preliminary behavioral experiments and mesoscale imaging in anesthetized mice.
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