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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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In the citing paper
“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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An adaptable, reusable, and light implant for chronic Neuropixels probesPreprint
Bimbard, C., Takács, F., Catarino, J., Fabre, J. M., Gupta, S., Lenzi, S. C., Melin, M. D., O’Neill, N., Oršolić, I., Robacha, M., et al. (2024) · eLife · doi:10.7554/elife.98522 · Cited by 15
“In particular, the only published recoverable implants for Neuropixels 2.0 probes may be too heavy for use with typical mice, and cannot be adjusted for different implantation trajectories (Steinmetz et al., 2021; van Daal et al., 2021).”
InfluentialSelf-citationSpike sorting biases and information loss in a detailed cortical modelPreprint
Laquitaine, S., Imbeni, M., Tharayil, J., Isbister, J. B., & Reimann, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.04.626805 · Cited by 23
Brown, S. T., Holla, M. R., Land, M. A., Yang, S., McDonald, A. J., St-Pierre, F., & Raman, I. M. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116148 · Cited by 12
Foraging as an ethological framework for neuroscience
Grima, L. L., Haberkern, H., Mohanta, R., Morimoto, M. M., Rajagopalan, A. E., & Scholey, E. V. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.08.006 · Cited by 15
Ide, K., & TAKAHASHI, S. Y. (2022) · Micromachines · doi:10.3390/mi13091529 · Cited by 12
Compression strategies for large-scale electrophysiology data
Buccino, A. P., Winter, O., Bryant, D., Feng, D. H., Svoboda, K., & Siegle, J. H. (2023) · Journal of Neural Engineering · doi:10.1088/1741-2552/acf5a4 · Cited by 17
“With the development, commercialization, and distribution of CMOS-based neural probes such as Neuropixels (Jun et al. 2017; Steinmetz et al. 2021),1 neuroscientists can now record brain function at unprecedented scales, accelerating progress towards a better understanding of the nervous system (Churchland et al. 2007).”
BackgroundInfluentialSelf-citationBrain state transitions primarily impact the spontaneous rate of slow-firing neurons
Dearnley, B., Jones, M., Dervinis, M., & Okun, M. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113185 · Cited by 11
Self-citationClosed-loop experiments and brain machine interfaces with multiphoton microscopy
Hira, R. (2024) · Neurophotonics · doi:10.1117/1.nph.11.3.033405 · Cited by 10
Multifunctional ultraflexible neural probe for wireless optogenetics and electrophysiology
Wang, S., Li, L., Zhang, S., Jiang, Q., Li, P., Wang, C., Xiao, R., Li, X., & Song, J. (2024) · Giant · doi:10.1016/j.giant.2024.100272 · Cited by 11
Self-citationNilsen, A. S., Arena, A., & Storm, J. F. (2024) · Neuroscience of Consciousness · doi:10.1093/nc/niae021 · Cited by 16
“Animal models also allow high-resolution methods such as silicon probes with high-density electrode arrays (e.g. neuropixels; Steinmetz et al. 2021) and in vivo whole-cell patch-clamp recordings (Noguchi et al. 2021), which can further elucidate mechanisms at the columnar or neural level,…”
MethodInference of monosynaptic connections from parallel spike trains: A review
Kobayashi, R., & Shinomoto, S. (2024) · Neuroscience Research · doi:10.1016/j.neures.2024.07.006 · Cited by 11
“In recent years, it has become possible to record spike signals from multiple neurons in parallel, and the number of such neurons has increased over the years, now exceeding a thousand (Stevenson and Kording, 2011; Steinmetz et al., 2021).”
BackgroundDevelopment of Higher-Level Vision: A Network Perspective
Bourne, J. A., Cichy, R. M., Kiorpes, L., Morrone, M. C., Arcaro, M. J., & Nielsen, K. J. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1291-24.2024 · Cited by 11
How can ethology inform the neuroscience of fear, aggression and dominance?
Battivelli, D., Fan, Z., Hu, H., & Gross, C. T. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00858-2 · Cited by 11
“It facilitates high-resolution, large-scale recording of hundreds of neurons simultaneously across various brain regions and has started to be applied in freely moving animals 121 .”
Hippocampal Neural Dynamics and Postoperative Delirium–like Behavior in Aged Mice
Guo, S., Yang, L., Ding, W., Dagnew, T. M., Gao, Y., Wang, W., Wang, P., Huang, S., Ran, C., Wang, C., et al. (2025) · Anesthesiology · doi:10.1097/aln.0000000000005478 · Cited by 11
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“By monolithically integrating an optical waveguide layer into CMOSelectrophysiologicalprobes 37,38 ,nanophotonicneuralprobeswithup to 960 microelectrodes were recently reported 30 .”
Gavornik, J. P., & Bear, M. F. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103019 · Cited by 11
Electrode pooling can boost the yield of extracellular recordings with switchable silicon probes
Lee, K. H., Ni, Y., Colonell, J. I., Karsh, B., Putzeys, J., Pachitariu, M., Harris, T. D., & Meister, M. (2021) · Nature Communications · doi:10.1038/s41467-021-25443-4 · Cited by 10
Self-citationBianco, M., Pisanello, M., Balena, A., Montinaro, C., Pisano, F., Spagnolo, B., Sabatini, B. L., Vittorio, M. D., & Pisanello, F. (2022) · APL Photonics · doi:10.1063/5.0073594 · Cited by 11
Guardamagna, M., Eichler, R., Pedrosa, R., Aarts, A. A. A., Meyer, A. F., & Battaglia, F. P. (2022) · Journal of Neural Engineering · doi:10.1088/1741-2552/ac6771 · Cited by 12
Sukman, L. J., & Stark, E. (2022) · eNeuro · doi:10.1523/eneuro.0265-22.2022 · Cited by 11
A miniaturized and low-energy subcutaneous optical telemetry module for neurotechnology
Xu, Z., Truong, N. D., Nikpour, A., & Kavehei, O. (2023) · Journal of Neural Engineering · doi:10.1088/1741-2552/acd147 · Cited by 13
“With the advancement of integrated circuits and materials, the state-of-the-art neuro signal sensor implants for animal research have 768 electrodes in a 750 × 720 μm2 area and can record 10 240 sites from two probes [2].”
BackgroundRobust Online Multiband Drift Estimation in Electrophysiology Data
Windolf, C., Paulk, A. C., Kfir, Y., Trautmann, E. M., Garcia, S., Meszéna, D., Muñoz, W., Hardstone, R., Caprara, I., Jamali, M., et al. (2023) · IEEE International Conference on Acoustics Speech and Signal Processing · doi:10.1109/icassp49357.2023.10095487 · Cited by 11
Hong, N., Kim, B., Lee, J., Choe, H. K., Jin, K. H., & Kang, H. (2024) · Nature Communications · doi:10.1038/s41467-024-44794-2 · Cited by 12
“Moreover, considering the recent efforts to increase the number of recording electrodes 4 – 6 , it would allow the collection of neuronal signals from more electrodes or for a longer duration within the same hardware resources.”
BackgroundResultInspiratory rhythm generation is stabilized by Ih
Burgraff, N. J., Phillips, R. S., Severs, L. J., Bush, N. E., Baertsch, N. A., & Ramirez, J. (2022) · Journal of Neurophysiology · doi:10.1152/jn.00150.2022 · Cited by 11
A Bandwidth-Efficient Emulator of Biologically-Relevant Spiking Neural Networks on FPGA
Leone, G., Raffo, L., & Meloni, P. (2022) · IEEE Access · doi:10.1109/access.2022.3192826 · Cited by 11
Frontal cortex learns to add evidence across modalitiesPreprint
Coen, P., Sit, T. P. H., Wells, M. J., Carandini, M., & Harris, K. D. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.26.441250 · Cited by 12
Self-citationSpike sorting: new trends and challenges of the era of high-density probesPreprint
Buccino, A. P., Garcia, S., & Yger, P. (2022) · doi:10.31219/osf.io/jhau2 · Cited by 11
Active Neural Interface Circuits and Systems for Selective Control of Peripheral Nerves: A Review
Habibollahi, M., Jiang, D., Lancashire, H. T., & Demosthenous, A. (2024) · IEEE Transactions on Biomedical Circuits and Systems · doi:10.1109/tbcas.2024.3430038 · Cited by 11
“Neural probes enable high-density interfacing with minimum invasiveness using a narrow, rigid shank, which can accommodate hundreds to thousands of pixels or electrode sites for recording [17], [73] or stimulating [74], [75] neural activity.”
Liu, N., Shiravi, S., Jin, T., Liu, J., Zhu, Z., Li, J., Cheung, I., Zhang, H., Wang, Y., Li, Q., et al. (2026) · Nature Biomedical Engineering · doi:10.1038/s41551-026-01620-y · Cited by 14
“These findings suggest a paradigm for organoid neural circuit research based on spatial electrophysiology, distinct from that for in vivo models 39,40 .”
Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents
Horváth, C., Ulbert, I., & Fiáth, R. (2023) · NeuroImage · doi:10.1016/j.neuroimage.2023.120484 · Cited by 10
Surface Functionalized Titanium Nitride Electrode for CMOS Compatible Bioelectronic Devices
Yu, M. S., Tang, X., Yang, S., Li, Z., Chen, C. Q., & Xie, S. (2024) · ChemMedChem · doi:10.1002/cmdc.202400189 · Cited by 11
Preconfigured architecture of the developing mouse brain
Chini, M., Hnida, M., Kostka, J. K., Chen, Y., & Hanganu‐Opatz, I. L. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114267 · Cited by 11
McKissick, O. P., Klimpert, N., Ritt, J. T., & Fleischmann, A. (2024) · Frontiers in Neural Circuits · doi:10.3389/fncir.2024.1414452 · Cited by 10
“New indicators and better imaging technologies are rapidly being developed (89–92), while the channel count of electrophysiological recording has dramatically increased (93, 94).”
BackgroundPrefrontal cortex neurons encode ambient light intensity differentially across regions and layers
Zangen, E., Hadar, S., Lawrence, C., Obeid, M., Rasras, H., Hanzin, E., Aslan, O., Zur, E., Schulcz, N., Cohen-Hatab, D., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49794-w · Cited by 11
Phalip, A., Netser, S., & Wagner, S. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105856 · Cited by 12
Balena, A., Bianco, M., Andriani, M. S., Montinaro, C., Spagnolo, B., Pisanello, M., Pisano, F., Sabatini, B. L., Vittorio, M. D., & Pisanello, F. (2025) · Nature Protocols · doi:10.1038/s41596-024-01105-9 · Cited by 12
fMRI data acquisition and analysis for task-free, anesthetized rats
Vrooman, R. M., van den Berg, M., Desrosiers-Grégoire, G., van Engelenburg, W. A., Galteau, M. E., Lee, S., Veltien, A. A., Barrière, D. A., Cash, D., Chakravarty, M. M., et al. (2025) · Nature Protocols · doi:10.1038/s41596-024-01110-y · Cited by 11
A Compact Low-Power Chopper Low Noise Amplifier for High Density Neural Front-Ends
Fava, A., Centurelli, F., Monsurrò, P., & Scotti, G. (2025) · Sensors · doi:10.3390/s25041157 · Cited by 10
“The single-shank of Neuropixel probes developed by IMEC [4], and the four-shank based on SiNAPS technology developed by IIT [6] are two examples of commercially available high-density probes.”
Low-cost, high-efficiency double-sided neural probe
Lee, H., Park, S., Kim, M. S., Lee, J., Lee, S., Chou, N., & Shin, H. (2025) · Sensors and Actuators A Physical · doi:10.1016/j.sna.2025.116437 · Cited by 10
Akhoundi, A., Landbrug, Y., Yan, P., Chichilnisky, E. J., Murmann, B., & Muratore, D. G. (2025) · Digest of technical papers/Digest of technical papers - IEEE International Solid-State Circuits Conference · doi:10.1109/isscc49661.2025.10904780 · Cited by 10
Bioelectrodes for high-channel count and small form factor CMOS neural probes
Ribeiro, J. F., Boi, F., Lecomte, A., Angotzi, G. N., & Berdondini, L. (2021) · International IEEE/EMBS Conference on Neural Engineering · doi:10.1109/ner49283.2021.9441160 · Cited by 10
Linking brain activity across scales with simultaneous opto- and electrophysiology
Hoffmann, A., & Helmchen, F. (2023) · Neurophotonics · doi:10.1117/1.nph.11.3.033403 · Cited by 12
“59,60 With single-wire electrodes, the typical yield is one to three isolated units; however, dense arrays are better able to distinguish the activity of intermingled neurons.”
Background
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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