Cortical Pyramidal and Parvalbumin Cells Exhibit Distinct Spatiotemporal Extracellular Electric Potentials

Brain circuits are composed of diverse cell types with distinct morphologies, connections, and distributions of ion channels. Modeling suggests that the spatial distribution of the extracellular voltage during a spike de-pends on cellular morphology, connectivity, and identity. However, experimental evidence from the intact brain is lacking. Here, we combined high-density recordings from hippocampal region CA1 and neocortex of freely moving mice with optogenetic tagging of parvalbumin-immunoreactive (PV) cells. We used ground truth tagging of the recorded pyramidal cells (PYR) and PV cells to construct binary classification models. Features derived from single-channel waveforms or from spike timing alone allowed near-perfect classification of PYR and PV cells. To determine whether there is unique information in the spatial distribution of the extracellular poten-tials, we removed all single-channel waveform information from the multichannel waveforms using an event-based delta-transformation. We found that spatiotemporal features derived from the transformed waveforms yield accurate classification. The extracellular analog of the spatial distribution of the initial depolarization phase provided the highest contribution to the spatially based prediction. Compared with PV cell spikes, PYR spikes exhibited higher spatial synchrony at the beginning of the extracellular spike and lower synchrony at the trough. The successful classification of PYR and PV cells based on purely spatial features provides direct experimental evidence that spikes of distinct cell types are associated with distinct spatial distributions of extracellular potentials.