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Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.
Open accessPublished version of a preprint
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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Activity in primate visual cortex is minimally driven by spontaneous movements
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“67) followed by manual curation in Python (www. github.com/cortex-lab/phy) for data from M1 and using the Plexon Offline Sorter (v.3.3.5; Plexon Inc.) for data from M2.”
MethodInfluentialSignal acquisition of brain–computer interfaces: A medical-engineering crossover perspective review
Sun, Y., Chen, X., Liu, B., Liang, L., Wang, Y., Gao, S., & Gao, X. (2024) · Fundamental Research · doi:10.1016/j.fmre.2024.04.011 · Cited by 74
“Notably, in 2021, researchers introduced Neuropixels 2.0, which enables more stable and prolonged recording compared to its pre-decessor [167] .”
InfluentialMultiregion neuronal activity: the forest and the trees
Machado, T. A., Kauvar, I., & Deisseroth, K. A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00634-0 · Cited by 71
Sibille, J., Gehr, C., Benichov, J. I., Balasubramanian, H., Teh, K. L., Lupashina, T., Vallentin, D., & Kremkow, J. (2022) · Nature Communications · doi:10.1038/s41467-022-32775-2 · Cited by 71
Vomero, M., Ciarpella, F., Zucchini, E., Kirsch, M., Fadiga, L., Stieglitz, T., & Asplund, M. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2022.121372 · Cited by 65
Flexible, scalable, high channel count stereo-electrode for recording in the human brain
Lee, K., Paulk, A. C., Ro, Y. G., Cleary, D. R., Tonsfeldt, K. J., Kfir, Y., Pezaris, J. S., Tchoe, Y., Lee, J., Bourhis, A. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-43727-9 · Cited by 67
“Other electrodes that can record single units from the human brain and afford high-resolution spatial mapping of single-cell activity include the Utah array 19 and Neuropixels 20,21 with up to hundreds of channels 22,23 .”
BackgroundMetal microdrive and head cap system for silicon probe recovery in freely moving rodent
Vöröslakos, M., Petersen, P. C., Vöröslakos, B., & Buzsáki, G. (2021) · eLife · doi:10.7554/elife.65859 · Cited by 64
“…in many experiments, where the relationship between neuronal activity and movement, perception, learning and memory, decision making, and other forms of cognition are studied to disambiguate overt behavior and hidden variables (Juavinett et al., 2019; Jun et al., 2017; Steinmetz et al., 2020).”
BackgroundInterfacing Biology and Electronics with Memristive Materials
Tzouvadaki, I., Gkoupidenis, P., Vassanelli, S., Wang, S., & Prodromakis, T. (2023) · Advanced Materials · doi:10.1002/adma.202210035 · Cited by 64
Self-citationHectoSTAR μLED Optoelectrodes for Large‐Scale, High‐Precision In Vivo Opto‐Electrophysiology
Vöröslakos, M., Kim, K., Slager, N., Ko, E., Oh, S., Parizi, S. S., Hendrix, B., Seymour, J. P., Wise, K. D., Buzsáki, G., et al. (2022) · Advanced Science · doi:10.1002/advs.202105414 · Cited by 60
Grid-cell modules remain coordinated when neural activity is dissociated from external sensory cues
Waaga, T., Agmon, H., Normand, V. A., Nagelhus, A., Gardner, R. J., Moser, M., Moser, E. I., & Burak, Y. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.011 · Cited by 61
Self-citationAdvocating for neurodata privacy and neurotechnology regulation
Yuste, R. (2023) · Nature Protocols · doi:10.1038/s41596-023-00873-0 · Cited by 75
“The procedure details how to use a modified electrical probe 2 to record neuronal activity during tumor resections and deep brain stimulation (DBS) electrode placements in patients with Parkinson’s disease.”
MethodLeft–right-alternating theta sweeps in entorhinal–hippocampal maps of space
Vollan, A. Z., Gardner, R. J., Moser, M., & Moser, E. I. (2025) · Nature · doi:10.1038/s41586-024-08527-1 · Cited by 89
“Instruments and procedures were similar to those described for Neu-ropixels recordings used in the lab 5,26,27,68 .”
InfluentialSelf-citationAccurate Localization of Linear Probe Electrode Arrays across Multiple Brains
Liu, L. D., Chen, S., Hou, H., West, S. J., Faulkner, M., Economo, M. N., Li, N., & Svoboda, K. (2021) · eNeuro · doi:10.1523/eneuro.0241-21.2021 · Cited by 53
“Neuropixels probes (Jun et al., 2017; Steinmetz et al., 2021) provide recordings across 960 recording electrodes distributed over 9.6 mm shanks.”
BackgroundInfluentialSelf-citationMulti-Regional Module-Based Signal Transmission in Mouse Visual Cortex
Jia, X., Siegle, J. H., Durand, S., Heller, G. R., Ramirez, T. K., Koch, C., & Olsen, S. R. (2021) · Neuron · doi:10.1016/j.neuron.2022.01.027 · Cited by 61
Long-term stability of single neuron activity in the motor system
Jensen, K. T., Harpaz, N. K., Dhawale, A. K., Wolff, S. B. E., & Ölveczky, B. P. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01194-3 · Cited by 56
“We therefore expect that our understanding of neural stability will benefit further from recent impressive advances in recording technology (Chung et al., 2019; Hong and Lieber, 2019; Steinmetz et al., 2021), especially if such advances can eventually be combined with methods for chronic recordings to track changes in…”
MethodNeural interface systems with on-device computing: machine learning and neuromorphic architectures
Yoo, J., & Shoaran, M. (2021) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.10.012 · Cited by 58
Borden, P. Y., Wright, N. C., Morrissette, A. E., Jaeger, D., Haider, B., & Stanley, G. B. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.008 · Cited by 54
Park, Y., Chung, T. S., Lee, G., & Rogers, J. A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00639 · Cited by 62
Mouse frontal cortex mediates additive multisensory decisions
Coen, P., Sit, T. P. H., Wells, M. J., Carandini, M., & Harris, K. D. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.008 · Cited by 60
Self-citationObject-centered population coding in CA1 of the hippocampus
Nagelhus, A., Andersson, S. O., Cogno, S. G., Moser, E. I., & Moser, M. (2023) · Neuron · doi:10.1016/j.neuron.2023.04.008 · Cited by 54
Self-citationCell-type-specific propagation of visual flicker
Schneider, M., Τζάνου, Α., Uran, C., & Vinck, M. A. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112492 · Cited by 61
How our understanding of memory replay evolves
Chen, Z. S., & Wilson, M. A. (2023) · Journal of Neurophysiology · doi:10.1152/jn.00454.2022 · Cited by 68
First Organoid Intelligence (OI) workshop to form an OI community
Pantoja, I. E. M., Smirnova, L., Muotri, A. R., Wahlin, K. J., Kahn, J., Boyd, J. L., Gracias, D. H., Harris, T. D., Cohen‐Karni, T., Caffo, B. S., et al. (2023) · Frontiers in Artificial Intelligence · doi:10.3389/frai.2023.1116870 · Cited by 60
“0 probes (Steinmetz et al., 2021), which are small enough to accommodate more than 10,000 channels in a freely moving mouse.”
BackgroundSelf-citationTracking neurons across days with high-density probes
van Beest, E. H., Bimbard, C., Fabre, J. M., Dodgson, S. W., Takács, F., Coen, P., Lebedeva, A., Harris, K. D., & Carandini, M. (2024) · Nature Methods · doi:10.1038/s41592-024-02440-1 · Cited by 61
“To develop and test UnitMatch, we used 1,350 recordings performed over multiple days (up to 235 days from a single probe) in mice implanted with chronic Neuropixels probes 31,35,41 in multiple brain regions including cortex, hippocampus, striatum and superior colliculus (Extended Data Table 1).”
InfluentialSelf-citationEmerging imaging methods to study whole-brain function in rodent models
Markicevic, M., Savvateev, I., Grimm, C., & Zerbi, V. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01575-5 · Cited by 55
Solving brain circuit function and dysfunction with computational modeling and optogenetic fMRI
Lee, J. H., Liu, Q., & Dadgar‐Kiani, E. (2022) · Science · doi:10.1126/science.abq3868 · Cited by 59
Multi-State Memristors and Their Applications: An Overview
Wang, C., Si, Z., Jiang, X., Malik, A., Pan, Y., Stathopoulos, S., Serb, A., Wang, S., Prodromakis, T., & Papavassiliou, C. (2022) · IEEE Journal on Emerging and Selected Topics in Circuits and Systems · doi:10.1109/jetcas.2022.3223295 · Cited by 52
“The state-of-the-art neural probe technologies today support implantation of over 10,000 microelectrodes acquiring a large volume of data from the brain [86], [87].”
BackgroundSelf-citationMultimodal Charting of Molecular and Functional Cell States via in situ Electro-Seq
Li, Q., Lin, Z., Liu, R., Tang, X., Huang, J., He, Y., Sui, X., Tian, W., Shen, H., Zhou, H., et al. (2022) · Cell · doi:10.1016/j.cell.2023.03.023 · Cited by 53
Acute head-fixed recordings in awake mice with multiple Neuropixels probes
Durand, S., Heller, G. R., Ramirez, T. K., Luviano, J., Williford, A., Sullivan, D. T., Cahoon, A., Farrell, C., Groblewski, P. A., Bennett, C., et al. (2022) · Nature Protocols · doi:10.1038/s41596-022-00768-6 · Cited by 56
The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo
Yu, C., Yu, Y., Adsit, L. M., Chang, J. T.-H., Barchini, J., Moberly, A. H., Benisty, H., Kim, J., Young, B., Heng, K., et al. (2023) · Nature Methods · doi:10.1038/s41592-023-02098-1 · Cited by 47
Abe, T., Kinsella, I., Saxena, S., Buchanan, E. K., Couto, J., Briggs, J., Kitt, S. L., Glassman, R., Zhou, J., Paninski, L., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.018 · Cited by 54
Nonlinear manifolds underlie neural population activity during behaviourPreprint
Fortunato, C., Bennasar-Vázquez, J., Park, J., Chang, J. C., Miller, L. E., Dudman, J. T., Perich, M. G., & Gallego, J. Á. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.18.549575 · Cited by 53
Self-citationEngineering strategies towards overcoming bleeding and glial scar formation around neural probes
Otte, E., Vlachos, A., & Asplund, M. (2022) · Cell and Tissue Research · doi:10.1007/s00441-021-03567-9 · Cited by 54
Curiosity-driven exploration: foundations in neuroscience and computational modeling
Modirshanechi, A., Kondrakiewicz, K., Wulfram Gerstner, B., & Haesler, S. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.10.002 · Cited by 50
“It is thus crucial to collect high-resolution neural data [120] to begin to understand how dynamic signals in neural circuits implement computations related to curiosity.”
Self-citationWireless Battery-free and Fully Implantable Organ Interfaces
Bhatia, A., Hanna, J., Stuart, T., Kasper, K. A., Clausen, D. M., & Gutruf, P. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00425 · Cited by 50
Tian, G., Liu, Y., Yu, M., Liang, C., Yang, D., Huang, J., Zhao, Q., Zhang, W., Chen, J., Wang, Y., et al. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c18983 · Cited by 49
Durá-Bernal, S., Neymotin, S. A., Suter, B. A., Dacre, J., Moreira, J. V. S., Urdapilleta, E., Schiemann, J. M., Duguid, I., Shepherd, G. M., & Lytton, W. W. (2022) · Cell Reports · doi:10.1016/j.celrep.2023.112574 · Cited by 48
Beau, M., Herzfeld, D. J., Naveros, F., Hemelt, M. E., D’Agostino, F., Oostland, M., Sánchez‐López, Á., Chung, Y. Y., Maibach, M., Kyranakis, S., et al. (2025) · Cell · doi:10.1016/j.cell.2025.01.041 · Cited by 55
Self-citationHenschke, J. U., & Pakan, J. M. P. (2023) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2023.1165307 · Cited by 58
“This has arisen from the development of advanced microscopy and electrophysiological techniques for recording neural activity while simultaneously probing and manipulating circuit elements (Dombeck et al., 2007; Fois et al., 2014; Steinmetz et al., 2021).”
MethodMicroscale Physiological Events on the Human Cortical Surface
Paulk, A. C., Yang, J. C., Cleary, D. R., Soper, D. J., Halgren, M., O’Donnell, A. R., Lee, S., Ganji, M., Ro, Y. G., Oh, H., et al. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab040 · Cited by 47
“…recording (including novel microelectrodes) and analytic approaches have been used to explore axonal action potentials (Robbins et al. 2013; Stuart and Spruston 2015; Jun et al. 2017), dendritic calcium spikes (Ross 2015; Suzuki and Larkum 2017; Golding et al. 2018), and backpropagating…”
BackgroundMethod
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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