Modern large-scale multineuronal recording methodologies, including multielectrode arrays, calcium imaging, and optogenetic techniques, produce single-neuron resolution data of a magnitude and precision that were the realm of science fiction twenty years ago. The major bottlenecks in systems and circuit neuroscience no longer lie in simply collecting data from large neural populations, but also in understanding this data: developing novel scientific questions, with corresponding analysis techniques and experimental designs to fully harness these new capabilities and meaningfully interrogate these questions. Advances in methods for signal processing, network analysis, dimensionality reduction, and optimal control -developed in lockstep with advances in experimental neurotechnology --promise major breakthroughs in multiple fundamental neuroscience problems. These trends are clear in a broad array of subfields of modern neuroscience; this review focuses on recent advances in methods for analyzing neural time-series data with single-neuronal precision. Topics reviewed herein are indicated in black..
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I. High-throughput neural signal processing methodsNeuroscientists have long dreamed of recording from many thousands of neurons simultaneously. This goal is the major motivation of the BRAIN initiative and related efforts, and with new calcium imaging methods and large-scale multielectrode array (MEA) devices, this dream is quickly becoming a reality. But now a major bottleneck exists. Cutting-edge calcium imaging methods and MEAs output data at rates on the order of terabytes/hour , and data rates continue to increase. At these huge rates processing and even storing the data is challenging (Freeman et al 2014 Nature Methods), let alone optimally extracting all the useful information in these data streams; without the right analytical technology, we will never unlock the true potential of these experimental advances.
Calcium imagingCalcium imaging has become the dominant method for recording from large populations of neurons, due to several well-known advantages: calcium imaging offers cell-type specificity and can be coupled easily with a variety of genetic tools; imaging approaches can be less invasive and damaging to brain tissue than inserting an MEA; calcium imaging has proven scalability to record simultaneously from O(10 4 ) neurons in vivo (over an order of magnitude larger than achieved by an MEA to date); and finally, imaging approaches enable significantly greater experimental design flexibility than MEAs in terms of which subsets of neurons in the imaging volume are interrogated at which times, and how many pixels are assigned to each neuron (we expand on the importance of this point below). At the same time, calcium imaging suffers from some clear disadvan...