Wide-Field Calcium Imaging of Neuronal Network Dynamics In Vivo

SIMPLE SUMMARY: We review advances in the properties of calcium sensors, microscopy, and data analysis that have brought about the ability to image large contiguous regions of the mouse brain, often termed wide-field or mesoscale imaging. We summarize representative wide-field imaging studies spanning several neuroscience subfields, providing an overview of insights gained into brain function. Finally, we present new developments in wide-field imaging that allow for more comprehensive investigation of activity across the brain. ABSTRACT: A central tenet of neuroscience is that sensory, motor, and cognitive behaviors are generated by the communications and interactions among neurons, distributed within and across anatomically and functionally distinct brain regions. Therefore, to decipher how the brain plans, learns, and executes behaviors requires characterizing neuronal activity at multiple spatial and temporal scales. This includes simultaneously recording neuronal dynamics at the mesoscale level to understand the interactions among brain regions during different behavioral and brain states. Wide-field Ca(2+) imaging, which uses single photon excitation and improved genetically encoded Ca(2+) indicators, allows for simultaneous recordings of large brain areas and is proving to be a powerful tool to study neuronal activity at the mesoscopic scale in behaving animals. This review details the techniques used for wide-field Ca(2+) imaging and the various approaches employed for the analyses of the rich neuronal-behavioral data sets obtained. Also discussed is how wide-field Ca(2+) imaging is providing novel insights into both normal and altered neural processing in disease. Finally, we examine the limitations of the approach and new developments in wide-field Ca(2+) imaging that are bringing new capabilities to this important technique for investigating large-scale neuronal dynamics.