Fully integrated silicon probes for high-density recording of neural activity
Open accessAbstract
Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca 2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal-oxide-semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.
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Neural activity was recorded using Neuropixels 1.0 silicon recording probes acutely inserted into the medial entorhinal cortex.
“During behavior, neural activity was recorded using Neuropixels 1.0 silicon recording probes (Jun et al., 2017), which were acutely inserted into the medial entorhinal cortex”
From Remapping in a recurrent neural network model of navigation and context inference (2023) · cites this paper as Jun et al., 2017
Normative models of remapping do not address how a biological system might implement the strategy.
“However, these normative models 29 (i.e., theories for why remapping occurs) do not address how a biological system might implement this strategy.”
From Remapping in a recurrent neural network model of navigation and context inference (2023) · cites this paper as [29]
Current state-of-the-art silicon-based in vivo systems do not commonly feature more than hundreds of electrodes, with recent improvements bringing this number closer to one thousand, even on a single probe.
“Current state-of-the-art silicon-based in vivo systems do not commonly feature more than hundreds of electrodes (Campbell et al. 1991), with recent improvements bringing this number closer to one thousand (Shobe et al. 2015; Scholvin et al. 2016; Buszáki et al. 2015), even on a single probe (Jun et al. 2017).”
From Realizing flexible bioelectronic medicines for accessing the peripheral nerves – technology considerations (2018) · cites this paper as Jun et al. 2017
The Neuropixels probe has a user-programmable switch that allows addressing 384 of the 960 sites simultaneously.
“In addition, it has a user-programmable switch that allows us to address 384 of the 960 sites simultaneously.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Jun et al., 2017
The Neuropixels probe is 10 mm long and contains 960 sites.
“The probe is 10 mm long and contains 960 sites.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Jun et al., 2017
The Neuropixels probe is the first report of a large (10 mm) dense (100 sites per millimeter) implantable nerve recording device.
“This is the first report of a large (10 mm) dense (100 sites per millimeter) implantable nerve recording device.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Jun et al., 2017
Titanium carbide (TiN) is selected as the recording site material, which is compatible with CMOS processing and has low and uniform impedance.
“Titanium carbide (TIN) is selected as the recording site material, which is compatible with CMOS processing and has the advantages of low and uniform impedance.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Jun et al., 2017
The researchers used two Neuropixels probes to record the activities of more than 700 neurons.
“The researchers used two Neuropixels probes to record the activities of more than 700 neurons.”
From Advances in Neural Recording and Stimulation Integrated Circuits (2021) · cites this paper as Jun et al., 2017
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- Authors
- Jun, J. J., Steinmetz, N. A., Siegle, J. H., Denman, D. J., Bauza, M., Barbarits, B., Lee, A. K., Anastassiou, C. A., Andrei, A., Aydın, Ç., Barbic, M., Blanche, T. J., Bonin, V., Couto, J., Dutta, B., Gratiy, S. L., Gutnisky, D. A., Häusser, M., Karsh, B., Ledochowitsch, P., Lopez, C. M., Mitelut, C., Musa, S., Okun, M., Pachitariu, M., Putzeys, J., Rich, P. D., Rossant, C., Sun, W.-L., Svoboda, K., Carandini, M., Harris, K. D., Koch, C., O’Keefe, J., & Harris, T. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- UCL Queen Square Institute of Neurology (GB)
- Allen Institute for Brain Science (US)
- IMEC (BE)
- Neuroelectronics Research Flanders (BE)
- University College London (GB)
- University of Leicester (GB)
- Corresponding author
- Harris, Timothy D.
- ORCID
- Steinmetz, Nicholas A.
- Siegle, Joshua H.
- Denman, Daniel J.
- Lee, Albert K.
- Anastassiou, Costas A.
- Andrei, Alexandru
- Aydın, Çağatay
- Barbic, Mladen
- Bonin, Vincent
- Couto, João
- Gratiy, Sergey L.
- Gutnisky, Diego A.
- Häusser, Michael
- Karsh, Bill
- Ledochowitsch, Peter
- Mitelut, Catalin
- Okun, Michael
- Pachitariu, Marius
- Putzeys, Jan
- Rossant, Cyrille
- Svoboda, Karel
- Carandini, Matteo
- Harris, Timothy D.
- Venue
- Nature
- Published
- 2017-11-09
- Volume
- 551
- Issue
- 7679
- Pages
- 232-236
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5955206
- OpenAlex
- W2767493192
- Cited by
- 2,190
- References
- 33
- Citations by year
- 2026: 229 · 2025: 334 · 2024: 269 · 2023: 297 · 2022: 232 · 2021: 289 · 2020: 221 · 2019: 199 · 2018: 116 · 2017: 2 · 2016: 1
- FWCI
- 71.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion, other-oa)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (203020/Z/16/Z, 095668, 095669, 100154)
- Academy of Medical Sciences (SBF002\1045)
- Biotechnology and Biological Sciences Research Council (BB/P020607/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Physical Sciences › Engineering › Biomedical Engineering › Analog and Mixed-Signal Circuit Design
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- Neuropixels, silicon probes, high-density neural recording, extracellular recording, single-unit recording, freely moving animals
- MeSH terms
- Animals, Electrodes, Female, Male, Movement, Neurons, Semiconductors, Silicon, Wakefulness, Prefrontal Cortex, Entorhinal Cortex, Mice, Rats
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