Understanding how assemblies of neurons encode information requires recording large populations of cells in the brain. In recent years, multi-electrode arrays and large silicon probes have been developed to record simultaneously from hundreds or thousands of electrodes packed with a high density. However, these new devices challenge the classical way to do spike sorting. Here we developed a new method to solve these issues, based on a highly automated algorithm to extract spikes from extracellular data, and show that this algorithm reached near optimal performance both in vitro and in vivo. The algorithm is composed of two main steps: 1) a "template-finding" phase to extract the cell templates, i.e. the pattern of activity evoked over many electrodes when one neuron fires an action potential; 2) a "template-matching" phase where the templates were matched to the raw data to find the location of the spikes. The manual intervention by the user was reduced to the minimal, and the time spent on manual curation did not scale with the number of electrodes. We tested our algorithm with large-scale data from in vitro and in vivo recordings, from 32 to 4225 electrodes. We performed simultaneous extracellular and patch recordings to obtain "ground truth" data, i.e. cases where the solution to the sorting problem is at least partially known. The performance of our algorithm was always close to the best expected performance. We thus provide a general solution to sort spikes from large-scale extracellular recordings.

Fast and accurate spike sorting in vitro and in vivo for up to thousands of electrodes