Spike sorting is a critical first step in extracting neural signals from large-scale electrophysiological data. This manuscript describes an efficient, reliable pipeline for spike sorting on dense multi-electrode arrays (MEAs), where neural signals appear across many electrodes and spike sorting currently represents a major computational bottleneck. We present several new techniques that make dense MEA spike sorting more robust and scalable. Our pipeline is based on an efficient multi-stage ''triage-then-cluster-then-pursuit'' approach that initially extracts only clean, high-quality waveforms from the electrophysiological time series by temporarily skipping noisy or ''collided'' events (representing two neurons firing synchronously). This is accomplished by developing a neural network detection method followed by efficient outlier triaging. The clean waveforms are then used to infer the set of neural spike waveform templates through nonparametric Bayesian clustering. Our clustering approach adapts a ''coreset'' approach for data reduction and uses efficient inference methods in a Dirichlet process mixture model framework to dramatically improve the scalability and reliability of the entire pipeline. The ''triaged'' waveforms are then finally recovered with matching-pursuit deconvolution techniques. The proposed methods improve on the state-of-the-art in terms of accuracy and stability on both real and biophysically-realistic simulated MEA data. Furthermore, the proposed pipeline is efficient, learning templates and clustering faster than real-time for a 500-electrode dataset, largely on a single CPU core.

Many neural circuits are composed of numerous distinct cell types that perform different operations on their inputs, and send their outputs to distinct targets. Therefore, a key step in understanding neural systems is to reliably distinguish cell types. An important example is the retina, for which present-day techniques for identifying cell types are accurate, but very labor-intensive. Here, we develop automated classifiers for functional identification of retinal ganglion cells, the output neurons of the retina, based solely on recorded voltage patterns on a large scale array. We use per-cell classifiers based on features extracted from electrophysiological images (spatiotemporal voltage waveforms) and interspike intervals (autocorrelations). These classifiers achieve high performance in distinguishing between the major ganglion cell classes of the primate retina, but fail in achieving the same accuracy in predicting cell polarities (ON vs. OFF). We then show how to use indicators of functional coupling within populations of ganglion cells (cross-correlation) to infer cell polarities with a matrix completion algorithm. This can result in accurate, fully automated methods for cell type classification.