Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra ( NP Ultra ). This device samples neuronal activity at ultra-high spatial density (∼10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron’s electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ∼3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior. ### Competing Interest Statement CK holds an executive position, and has a financial interest, in Intrinsic Powers, Inc., a company whose purpose is to develop a device that can be used in the clinic to assess the presence and absence of consciousness in patients. This does not pose any conflict of interest with regard to the work undertaken for this publication. BR, CML, and BD are employees of IMEC vzw, a nonprofit research institute that manufactures, sells, and distributes the Neuropixels probes, at cost, to the research community. IMEC vzw holds patents US10811542B2, US10044325B2, and US9384990B2 related to the Neuropixels 1.0 technology that is built upon in this work. All other authors have no competing interests.