  Measurements of neuronal activity across brain areas are important for
understanding the neural correlates of cognitive and motor processes like
attention, decision-making, and action selection. However, techniques that
allow cellular resolution measurements are expensive and require a high degree
of technical expertise, which limits their broad use. Widefield imaging of
genetically encoded indicators is a high throughput, cost effective, and
flexible approach to measure activity of specific cell populations with high
temporal resolution and a cortex-wide field of view. Here we outline our
protocol for assembling a widefield setup, a surgical preparation to image
through the intact skull, and imaging neural activity chronically in behaving,
transgenic mice that express a calcium indicator in specific subpopulations of
cortical neurons. Further, we highlight a processing pipeline that leverages
novel, cloud-based methods to analyze large-scale imaging datasets. The
protocol targets labs that are seeking to build macroscopes, optimize surgical
procedures for long-term chronic imaging, and/or analyze cortex-wide neuronal
recordings.
