Ultra-high-density Neuropixels probes improve detection and identification in neuronal recordings

Zhiwen Ye¹, Andrew M Shelton², Jordan R Shaker¹, Julien Boussard³, Jennifer Colonell⁴, Daniel Birman¹, Sahar Manavi⁵, Susu Chen⁴, Charlie Windolf³, Cole Hurwitz⁶, Han Yu⁷, Tomoyuki Namima⁸, Federico Pedraja⁶, Shahaf Weiss⁹, Bogdan C Raducanu¹⁰, Torbjørn V Ness¹¹, Xiaoxuan Jia¹², Giulia Mastroberardino¹³, L Federico Rossi¹⁴, Matteo Carandini¹⁵, Michael Häusser¹⁶, Gaute T Einevoll¹⁷, Gilles Laurent⁹, Nathaniel B Sawtell⁶, Wyeth Bair¹⁸, Anitha Pasupathy¹⁸, Carolina Mora Lopez¹⁰, Barundeb Dutta¹⁰, Liam Paninski³, Joshua H Siegle¹⁹, Christof Koch⁵, Shawn R Olsen², Timothy D Harris²⁰, Nicholas A Steinmetz²¹

Affiliations

¹ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA.
² MindScope Program, Allen Institute, Seattle, WA, USA; Allen Institute for Neural Dynamics, Seattle, WA, USA.
³ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Statistics, Columbia University, New York, NY, USA.
⁴ Janelia Research Campus, Ashburn, VA, USA.
⁵ MindScope Program, Allen Institute, Seattle, WA, USA.
⁶ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
⁷ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Electrical Engineering, Columbia University, New York, NY, USA.
⁸ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA; Graduate School of Frontier Biosciences, The University of Osaka, Suita, Japan; Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT), Suita, Japan.
⁹ Max Planck Institute for Brain Research, Frankfurt, Germany.
¹⁰ IMEC, Leuven, Belgium.
¹¹ Department of Physics, Norwegian University of Life Sciences, Ås, Norway.
¹² School of Life Sciences & IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.
¹³ UCL Institute of Ophthalmology, University College London, London, UK; Wolfson Institute for Biomedical Research, University College London, London, UK.
¹⁴ Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy.
¹⁵ UCL Institute of Ophthalmology, University College London, London, UK.
¹⁶ Wolfson Institute for Biomedical Research, University College London, London, UK; School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
¹⁷ Department of Physics, Norwegian University of Life Sciences, Ås, Norway; Department of Physics, University of Oslo, Oslo, Norway.
¹⁸ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
¹⁹ Allen Institute for Neural Dynamics, Seattle, WA, USA.
²⁰ Janelia Research Campus, Ashburn, VA, USA; Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA.
²¹ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA. Electronic address: nick.steinmetz@gmail.com.

PMID: 41033305
DOI: 10.1016/j.neuron.2025.08.030

Free article

Ultra-high-density Neuropixels probes improve detection and identification in neuronal recordings

Zhiwen Ye et al. Neuron. 2025.

Free article

. 2025 Sep 30:S0896-6273(25)00665-8.

doi: 10.1016/j.neuron.2025.08.030. Online ahead of print.

Authors

Affiliations

¹ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA.
² MindScope Program, Allen Institute, Seattle, WA, USA; Allen Institute for Neural Dynamics, Seattle, WA, USA.
³ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Statistics, Columbia University, New York, NY, USA.
⁴ Janelia Research Campus, Ashburn, VA, USA.
⁵ MindScope Program, Allen Institute, Seattle, WA, USA.
⁶ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
⁷ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Electrical Engineering, Columbia University, New York, NY, USA.
⁸ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA; Graduate School of Frontier Biosciences, The University of Osaka, Suita, Japan; Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT), Suita, Japan.
⁹ Max Planck Institute for Brain Research, Frankfurt, Germany.
¹⁰ IMEC, Leuven, Belgium.
¹¹ Department of Physics, Norwegian University of Life Sciences, Ås, Norway.
¹² School of Life Sciences & IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.
¹³ UCL Institute of Ophthalmology, University College London, London, UK; Wolfson Institute for Biomedical Research, University College London, London, UK.
¹⁴ Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy.
¹⁵ UCL Institute of Ophthalmology, University College London, London, UK.
¹⁶ Wolfson Institute for Biomedical Research, University College London, London, UK; School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
¹⁷ Department of Physics, Norwegian University of Life Sciences, Ås, Norway; Department of Physics, University of Oslo, Oslo, Norway.
¹⁸ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
¹⁹ Allen Institute for Neural Dynamics, Seattle, WA, USA.
²⁰ Janelia Research Campus, Ashburn, VA, USA; Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA.
²¹ Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA. Electronic address: nick.steinmetz@gmail.com.

PMID: 41033305
DOI: 10.1016/j.neuron.2025.08.030

Abstract

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). Using NP Ultra, neuronal yield in mouse visual cortex recordings increased by more than 2-fold. With ultra-high spatial resolution, we discovered that a feature of extracellular waveforms, the spatial extent or "footprint," distinguished axonal from somatic recordings. In addition, three genetically identified cortical cell types could be discriminated from one another with ∼80% accuracy and from other neurons with ∼85% accuracy. NP Ultra improves yield, detection of subcellular compartments, and cell type identification to enable a more powerful dissection of neural circuit activity during behavior.

Keywords: Neuropixels probe; cell type classification; extracellular electrophysiology; neuroscience; optotagging; probe design; subcellular recording; whole-brain mapping.

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Conflict of interest statement

Declaration of interests C.K. 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. B.R., C.M.L., and B.D. 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 NP 1.0 technology that is built upon in this work. M.C., M.H., and L.P. are members of Neuron's advisory board.

Update of

Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings.
Ye Z, Shelton AM, Shaker JR, Boussard J, Colonell J, Birman D, Manavi S, Chen S, Windolf C, Hurwitz C, Namima T, Pedraja F, Weiss S, Raducanu B, Ness TV, Jia X, Mastroberardino G, Rossi LF, Carandini M, Häusser M, Einevoll GT, Laurent G, Sawtell NB, Bair W, Pasupathy A, Lopez CM, Dutta B, Paninski L, Siegle JH, Koch C, Olsen SR, Harris TD, Steinmetz NA. Ye Z, et al. bioRxiv [Preprint]. 2024 Apr 10:2023.08.23.554527. doi: 10.1101/2023.08.23.554527. bioRxiv. 2024. Update in: Neuron. 2025 Sep 30:S0896-6273(25)00665-8. doi: 10.1016/j.neuron.2025.08.030. PMID: 37662298 Free PMC article. Updated. Preprint.

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Ultra-high-density Neuropixels probes improve detection and identification in neuronal recordings

Affiliations

Ultra-high-density Neuropixels probes improve detection and identification in neuronal recordings

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

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