RT Journal Article SR Electronic T1 Identification of cellular-activity dynamics across large tissue volumes in the mammalian brain JF bioRxiv FD Cold Spring Harbor Laboratory SP 132688 DO 10.1101/132688 A1 Grosenick, Logan A1 Broxton, Michael A1 Kim, Christina K. A1 Liston, Conor A1 Poole, Ben A1 Yang, Samuel A1 Andalman, Aaron A1 Scharff, Edward A1 Cohen, Noy A1 Yizhar, Ofer A1 Ramakrishnan, Charu A1 Ganguli, Surya A1 Suppes, Patrick A1 Levoy, Marc A1 Deisseroth, Karl YR 2017 UL http://biorxiv.org/content/early/2017/05/01/132688.abstract AB Tracking the coordinated activity of cellular events through volumes of intact tissue is a major challenge in biology that has inspired significant technological innovation. Yet scanless measurement of the high-speed activity of individual neurons across three dimensions in scattering mammalian tissue remains an open problem. Here we develop and validate a computational imaging approach (SWIFT) that integrates high-dimensional, structured statistics with light field microscopy to allow the synchronous acquisition of single-neuron resolution activity throughout intact tissue volumes as fast as a camera can capture images (currently up to 100 Hz at full camera resolution), attaining rates needed to keep pace with emerging fast calcium and voltage sensors. We demonstrate that this large field-of-view, single-snapshot volume acquisition method—which requires only a simple and inexpensive modification to a standard fluorescence microscope—enables scanless capture of coordinated activity patterns throughout mammalian neural volumes. Further, the volumetric nature of SWIFT also allows fast in vivo imaging, motion correction, and cell identification throughout curved subcortical structures like the dorsal hippocampus, where cellular-resolution dynamics spanning hippocampal subfields can be simultaneously observed during a virtual context learning task in a behaving animal. SWIFT’s ability to rapidly and easily record from volumes of many cells across layers opens the door to widespread identification of dynamical motifs and timing dependencies among coordinated cell assemblies during adaptive, modulated, or maladaptive physiological processes in neural systems.