Understanding the dynamic activity of neural circuits is central to the NIH BRAIN Initiative. This FOA seeks applications for proof-of-concept testing and development of new technologies and novel approaches for large scale recording and manipulation of neural activity, to enable transformative understanding of dynamic signaling in the nervous system. In particular we seek exceptionally creative approaches to address major challenges associated with recording and manipulating neural activity, with cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. It is expected that the proposed research may be high risk, but if successful could profoundly change the course of neuroscience research. Proposed technologies should be compatible with experiments in behaving animals, and should include advancements that enable or reduce major barriers to hypothesis driven experiments. Technologies may engage diverse types of signaling beyond neuronal electrical activity for large-scale analysis, and may utilize any modality such as optical, electrical, magnetic, acoustic or genetic recording/manipulation. Applications that seek to integrate multiple approaches are encouraged. Where appropriate, applications are expected to integrate appropriate domains of expertise, including biological, chemical and physical sciences, engineering, computational modeling and statistical analysis.