Comprehensive imaging of cortical networks

•We review advances in imaging activity in large neural populations.•Calcium imaging promises comprehensive activity measurement in entire brain regions.•Red-shifted, faster, and more sensitive protein indicators will drive future advances.•Structural markers help segmentation, counting, unbiased sampling, and typing.•Standardized, well-vetted approaches for data processing are urgently needed.

Neural computations are implemented by activity in spatially distributed neural circuits. Cellular imaging fills a unique niche in linking activity of specific types of neurons to behavior, over spatial scales spanning single neurons to entire brain regions, and temporal scales from milliseconds to months. Imaging may soon make it possible to track activity of all neurons in a brain region, such as a cortical column. We review recent methodological advances that facilitate optical imaging of neuronal populations in vivo, with an emphasis on calcium imaging using protein indicators in mice. We point out areas that are particularly ripe for future developments.