The brain is a three-dimensional, densely-wired circuit that computes via large sets of widely distributed neurons interacting at fast timescales. In order to understand the brain, ideally it would be possible to observe the electrical activity, and other intra- and intercellular signaling pathways, of many neurons—and ideally entire brains—with as great a degree of precision as possible, so as to understand the neural codes and dynamics that are produced by the circuits of the brain. Our lab and our collaborators are developing a number of innovations—such as new fluorescent reporters of cellular signals such as voltage, and new robotic and nanotechnological probes—to enable such analyses of neural circuit dynamics. These tools will hopefully enable pictures of how neurons work together to implement brain computations, and how these computations go awry in brain disorder states. Such neural observation strategies may also serve as detailed biomarkers of brain disorders or indicators of potential drug side effects. These technologies may, in conjunction with optogenetics, enable closed-loop neural control technologies, which can introduce information into the brain as a function of brain state ("brain co-processors"), enabling new kinds of circuit characterization tool as well as new kinds of advanced brain-repair prosthetic. To build these tools, we are developing supporting approaches such as robots and molecular strategies for multidimensional directed evolution of protein-based tools in mammalian cells.