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Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.
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Abstract
Recording many neurons for a long time: The ultimate aim of chronic recordings is to sample from the same neuron over days and weeks. However, this goal has been difficult to achieve for large populations of neurons. Steinmetz et al. describe the development and testing of Neuropixels 2.0. This new electrophysiological recording tool is a miniaturized, high-density probe for both acute and long-term experiments combined with sophisticated software algorithms for fully automatic post hoc computational stabilization. The technique also provides a strategy for extending the number of recorded sites beyond the number of available recording channels. In freely moving animals, extremely large numbers of individual neurons could thus be followed and tracked with the same probe for weeks and occasionally months. Science , this issue p. eabf4588
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“The weight of the probe plus a headstage is about 1.1 g.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“Using two four-shank probes, combined with a motion correction algorithm, the success rate of neuron tracking is more than 90% in 2 weeks and more than 80% successful for up to 2 months.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“Based on Neuropixels 1.0, the team has successfully developed a more miniaturized Neuropixels 2.0 with more recording sites.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“The length of the probe is still 10 mm and the number of recording sites per handle is 1,280.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“In the latest research, the problem of stable recording of a single neuron on a long-time scale from several weeks to several months has been overcome (Steinmetz et al., 2021).”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“The probe consists of four slices inserted into the brain and a probe base (the voltage signal is filtered, amplified, multiplexed, and digitized on the base).”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“Compared with the 20 μm of Neuropixels 1.0, the recording sites are arranged vertically in two columns rather than staggered, and the vertical distance from center to center is 15 μm.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
In the citing paper
“The four-shank version supports 5,120 recording sites and the headstage is miniaturized to about one-third of the size of those for Neuropixels 1.0, which is more suitable for chronic recording in a freely moving mouse.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Steinmetz et al., 2021
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“A natural extension of our framework would be to sample translaminar population activity across multiple locations with multiple shank silicon arrays (Steinmetz et al., 2021; Berdondini et al., 2024) and investigate the temporal coordination for retinotopic positions receiving similar visual input.”
BackgroundExtreme Mechanics of Hydrogels TowardIn SituHydrogel Bioelectronics
Wong, T. H., Zhao, X., & Lin, S. (2024) · Wiley eBooks · doi:10.1002/9783527842308.ch1 · Cited by 1
Redman, W. T., Acosta–Mendoza, S., Wei, X.-X., & Goard, M. J. (2024) · eLife · doi:10.7554/elife.100652.1 · Cited by 1
Simultaneous mesoscopic measurement and manipulation of mouse cortical activityPreprint
Matveev, P., Li, A. J., Ye, Z., Bowen, A. J., Opitz-Araya, X., Ting, J. T., & Steinmetz, N. A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.01.621418 · Cited by 2
Self-citationHigh-Resolution Laminar Identification in Macaque Primary Visual Cortex Using Neuropixels ProbesPreprint
Zhang, L. A., Li, P., & Callaway, E. M. (2024) · eLife · doi:10.7554/elife.97290.2 · Cited by 1
Cabral, H. V., Inglis, J. G., Pourreza, E., dos Santos, M. A., Cosentino, C., Ó’Reilly, D., Delis, I., & Negro, F. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.04.635938 · Cited by 1
Huang, H., Liu, Y., Yang, S., Hu, S. N., English, D. F., & Jia, X. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.29.662251 · Cited by 2
Response dynamics in macaque ventral stream recapitulate the visual hierarchy
Xiao, W., Causin, T., Vinken, K., & Livingstone, M. (2026) · eNeuro · doi:10.1101/2025.11.11.686115 · Cited by 2
Schiltz, E., Broux, M., Aydın, Ç., Gonçalves, P. J., & Haesler, S. (2025) · eLife · doi:10.7554/elife.103373.2 · Cited by 1
Self-citationNeuronal recordings in head-fixed and freely-moving mole-ratsPreprint
Shirdhankar, R. N., Saeedi, A., Fenton, G. E., Moritz, L., Jacob, P.-Y., Webb, L. M., Wolf-Kümmeth, S., Boenigk, W., Heinrichs, E., Begall, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.15.693140 · Cited by 1
“Chronic electrophysiology recordings enable the study of long-term dynamics of neural activity in behaving animals (Guan et al., 2019; Saeedi et al., 2024; Steinmetz et al., 2021).”
Mouse sensorimotor cortex reflects complex kinematic details during reaching and graspingPreprint
Grier, H. A., Salimian, S., & Kaufman, M. T. (2025) · eLife · doi:10.7554/elife.106270.1 · Cited by 1
Mouse sensorimotor cortex reflects complex kinematic details during reaching and graspingPreprint
Grier, H. A., Salimian, S., & Kaufman, M. T. (2026) · eLife · doi:10.7554/elife.106270.2 · Cited by 1
Opening the black box toward a modular approach to spike sortingPreprint
Garcia, S., Halcrow, C., Windolf, C., McKenzie, Z. M., Adkisson-Floro, P., Mayorquin, H. R., Dichter, B., Buccino, A. P., & Yger, P. (2026) · eLife · doi:10.7554/elife.110588 · Cited by 1
“With the development and widespread adoption of high-density microelectrode arrays both for in vivo ( Jun et al., 2017b ; Steinmetz et al., 2021 ; Angotzi et al., 2019 ) and in vitro applications ( Hua et al., 2025 ; Wolff et al., 2025 ; Schröter et al., 2025 ), automated solutions to the spike…”
Preventing Data Leakage in Neural DecodingPreprint
Wong, R., McCullough, M., Lu, T., Zhu, S., & Goodhill, G. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.26.701583 · Cited by 2
“Recent advances in recording techniques in animals now allow many thousands of neurons to be recorded simultaneously (Ahrens et al., 2013; Jun et al., 2017; Saxena & Cunningham, 2019; Steinmetz et al., 2021; Lin et al., 2022; Urai et al., 2022), resulting in complex and high-dimensional data.”
Efficient and reproducible pipelines for spike sorting large-scale electrophysiology dataPreprint
Buccino, A. P., Sridhar, A., Feng, D. H., Svoboda, K., & Siegle, J. H. (2026) · eLife · doi:10.7554/elife.110170 · Cited by 1
“5 was introduced in the publication describing Neuropixels 2.0 probes ( Steinmetz et al., 2021 ), and was incorporated into the original version of our spike sorting pipeline.”
InfluentialSelf-citationA multiplexed striatal architecture for generalized spatial goal progressPreprint
Takakuwa, N., Golipour, Z., & Ito, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.08.716650 · Cited by 1
“Using large-scale Neuropixels 42,43 recordings, fiber photometry to monitor dopamine concentration, and pharmacogenetic and optogenetic perturbations, we test whether the NAc serves as a substrate for computing generalized spatial states defined by physical distance to the goal, as predicted by…”
Place and behavioral modulation of hippocampal neurons during immobility
Sartorato, N., Zouridis, I. S., Narantsatsralt, U.-U., Blanco-Hernández, E., & Burgalossi, A. (2026) · Nature Communications · doi:10.1038/s41467-026-75492-w · Cited by 1
“Spike sorting was performed of fl ine with Kilosort 2.5 software 125 (https://github.com/MouseLand/ Kilosort) and the visualization for manual curation was performed in Phy2 (https://github.com/cortex-lab/phy) with the aid of extra plugin tools (https://zenodo.org/records/3367782).”
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“Recent technical advances in neuronal recording methodologies (such as Neuropixels probes; Jun et al. 2017; Steinmetz et al. 2020) allow recording of large numbers of single neurons within and between multiple brain regions simultaneously (Siegle et al. 2019; Stringer et al. 2019; Steinmetz et al.…”
BackgroundAn array of options for scaling up electrophysiology
Eisenstein, M. S. (2021) · Lab Animal · doi:10.1038/s41684-021-00758-3
Dias, C., Castro, D., Aroso, M., Ventura, J. O., & Aguiar, P. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.20.444941
“This means that memristive technology can leverage on the recent developments on high-density microelectrode arrays (MEAs) and neuronal probes carrying hundreds to thousands of recording/stimulating electrodes at an unprecedented spatiotemporal resolution.(17)”
BackgroundFlexible Corticospinal Control of Muscles
Marshall, N. J. (2021) · doi:10.7916/d8-3xfh-fd51
On the role of parvalbumin interneurons in neuronal network activity in the prefrontal cortex
Guyon, N. (2021) · Figshare
Meister, M. (2021) · CaltechAUTHORS (California Institute of Technology) · doi:10.48550/arxiv.2107.13532
“Multi-electrode arrays serve to record electrical signals of many neurons in the brain simultaneously [1, 2].”
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Flexibility of Behavior-Related Multidimensional Neural Activity
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Song Production Circuits in Songbirds Revealed by Intracellular Recordings
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“Arrays can now be fabricated that contain hundreds to thousands of densely packed electrode contacts spanning less than 10 square millimeters.(2) However, while electrophysiological recordings intrinsically have high temporal resolution on the scale of milliseconds, these arrays still only sample a small volume of tis…”
BackgroundUnsupervised Channel Compression Methods in Motor Prostheses Design
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“edu simultaneously record spiking activity from 758 sites out of 10,240 available sites across two 4-shank probes [10].”
MethodManipulation-specific activity in motor and somatosensory cortex as mice handle foodPreprint
Barrett, J., & Shepherd, G. (2022) · bioRxiv · doi:10.1101/2022.02.23.481687
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Circuits and mechanisms controlling SW-REM alternation in sleep
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Minimally-invasive and non-invasive flexible devices for robust characterizations of deep tissues
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Self-citationFunctional imaging of the anesthetized brain in primates and rodents
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Multichannel neural spike sorting with spike reduction and positional featurePreprint
Mohammadi, Z., Denman, D. J., Klug, A., & Lei, T. C. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.02.506385
Multimodal Charting of Molecular and Functional Cell States via in situ Electro-SeqPreprint
Li, Q., Lin, Z., Liu, R., Tang, X., Huang, J., He, Y., Sui, X., Tian, W., Zhou, H., Sheng, H., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4173435
Metadata
- Authors
- Steinmetz, N. A., Aydin, C., Lebedeva, A., Okun, M., Pachitariu, M., Bauza, M., Beau, M., Bhagat, J., Böhm, C., Broux, M., Chen, S., Colonell, J., Gardner, R. J., Karsh, B., Kloosterman, F., Kostadinov, D., Mora-Lopez, C., O’Callaghan, J., Park, J., Putzeys, J., Sauerbrei, B., van Daal, R. J. J., Vollan, A. Z., Wang, S., Welkenhuysen, M., Ye, Z., Dudman, J. T., Dutta, B., Hantman, A. W., Harris, K. D., Lee, A. K., Moser, E. I., O’Keefe, J., Renart, A., Svoboda, K., Häusser, M., Haesler, S., Carandini, M., & Harris, T. D.
- Affiliations
- University of Washington (US)
- Neuroelectronics Research Flanders, Leuven, Belgium.
- Sainsbury Wellcome Centre (GB)
- University of Leicester (GB)
- Howard Hughes Medical Institute (US)
- Sainsbury Wellcome Centre, University College London, London, UK.
- University College London (GB)
- UCL Queen Square Institute of Neurology (GB)
- Neuroelectronics Research Flanders (BE)
- Norwegian University of Science and Technology (NO)
- Vlaams Instituut voor Biotechnologie (BE)
- IMEC, Leuven, Belgium.
- IMEC (BE)
- Champalimaud Foundation (PT)
- Corresponding author
- Steinmetz, Nicholas A.
- Lebedeva, Anna
- Okun, Michael
- Pachitariu, Marius
- Carandini, Matteo
- Harris, Timothy D.
- ORCID
- Steinmetz, Nicholas A.
- Aydin, Cagatay
- Lebedeva, Anna
- Okun, Michael
- Pachitariu, Marius
- Bauza, Marius
- Beau, Maxime
- Bhagat, Jai
- Böhm, Claudia
- Broux, Martijn
- Chen, Susu
- Colonell, Jennifer
- Gardner, Richard J.
- Karsh, Bill
- Kloosterman, Fabian
- Kostadinov, Dimitar
- Park, Junchol
- Putzeys, Jan
- Sauerbrei, Britton
- van Daal, Rik J. J.
- Vollan, Abraham Z.
- Wang, Shiwei
- Welkenhuysen, Marleen
- Ye, Zhiwen
- Dudman, Joshua T.
- Hantman, Adam W.
- Lee, Albert K.
- Moser, Edvard I.
- O’Keefe, John
- Renart, Alfonso
- Svoboda, Karel
- Häusser, Michael
- Haesler, Sebastian
- Carandini, Matteo
- Harris, Timothy D.
- Venue
- Science
- Published
- 2021-04-16
- Volume
- 372
- Issue
- 6539
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8244810
- OpenAlex
- W3142226569
- Cited by
- 1,173
- References
- 81
- Citations by year
- 2026: 200 · 2025: 255 · 2024: 246 · 2023: 235 · 2022: 150 · 2021: 81
- FWCI
- 81.91
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Lirias (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- National Institutes of Health (1U01NS113252-01)
- Pew Charitable Trusts
- Kavli Foundation
- Esther A. and Joseph Klingenstein Fund
- ASCRS Research Foundation
- Wellcome (204915/Z/16/Z, 201225/Z/16/Z, 204717/Z/16/Z)
- Agentschap Innoveren en Ondernemen (1U01NS113252-01, G096219N, C14/17/109, G0D7516N, C14/17/042, BB/P020607/1, SBF002, HBC.2018.2114)
- Biotechnology and Biological Sciences Research Council
- Fonds Wetenschappelijk Onderzoek
- KU Leuven (C14/17/109)
- Vlaamse regering
- Fundação Champalimaud (204915/Z/16/Z, 951319, 295721, 286225, 223262)
- Koç Üniversitesi
- Research Council of Norway (National Infrastructure Scheme, NORBRAIN, grant number 295721, FRIPRO grant number 286225, Centre of Excellence grant number 223262)
- HHMI Janelia Research Campus
- Hermesfonds with a VLAIO Baekeland mandate (HBC.2018.2114)
- Sainsbury Wellcome Centre for Neural Circuits and Behaviour
- Research Foundation Flanders (G096219N)
- Academy of Medical Sciences and Wellcome Trust (Springboard SBF002\1045)
- BBSRC (BB/P020607/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chronic neural recording, miniaturized probe, site density, post-hoc correction, small mammals, mice, rats
- MeSH terms
- Action Potentials, Algorithms, Animals, Brain, Electrodes, Implanted, Electrophysiology, Male, Mice, Inbred C57BL, Microelectrodes, Miniaturization, Neurons, Mice, Rats
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