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Fully integrated silicon probes for high-density recording of neural activity.

ABSTRACT: 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 Ca2+ 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-?m 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.

SUBMITTER: Jun JJ

PROVIDER: S-EPMC5955206 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Fully integrated silicon probes for high-density recording of neural activity.

Jun James J JJ Steinmetz Nicholas A NA Siegle Joshua H JH Denman Daniel J DJ Bauza Marius M Barbarits Brian B Lee Albert K AK Anastassiou Costas A CA Andrei Alexandru A Aydın Çağatay Ç Barbic Mladen M Blanche Timothy J TJ Bonin Vincent V Couto João J Dutta Barundeb B Gratiy Sergey L SL Gutnisky Diego A DA Häusser Michael M Karsh Bill B Ledochowitsch Peter P Lopez Carolina Mora CM Mitelut Catalin C Musa Silke S Okun Michael M Pachitariu Marius M Putzeys Jan J Rich P Dylan PD Rossant Cyrille C Sun Wei-Lung WL Svoboda Karel K Carandini Matteo M Harris Kenneth D KD Koch Christof C O'Keefe John J Harris Timothy D TD

Nature 20171101 7679

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<sup>2+</sup> imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local f ...[more]

PMID: 29120427

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Project description:Optogenetic manipulations are widely used for investigating the contribution of genetically identified cell types to behavior. Simultaneous electrophysiological recordings are less common, although they are critical for characterizing the specific impact of optogenetic manipulations on neural circuits in vivo. This is at least in part because combining photostimulation with large-scale electrophysiological recordings remains technically challenging, which also poses a limitation for performing extracellular identification experiments. Currently available interfaces that guide light of the appropriate wavelength into the brain combined with an electrophysiological modality suffer from various drawbacks such as a bulky size, low spatial resolution, heat dissipation, or photovoltaic artifacts. To address these challenges, we have designed and fabricated an integrated ultrathin neural interface with 12 optical outputs and 24 electrodes. We used the device to measure the effect of localized stimulation in the anterior olfactory cortex, a paleocortical structure involved in olfactory processing. Our experiments in adult mice demonstrate that because of its small dimensions, our novel tool causes far less tissue damage than commercially available devices. Moreover, optical stimulation and recording can be performed simultaneously, with no measurable electrical artifact during optical stimulation. Importantly, optical stimulation can be confined to small volumes with approximately single-cortical layer thickness. Finally, we find that even highly localized optical stimulation causes inhibition at more distant sites. NEW & NOTEWORTHY In this study, we establish a novel tool for simultaneous extracellular recording and optogenetic photostimulation. Because the device is built using established microchip technology, it can be fabricated with high reproducibility and reliability. We further show that even very localized stimulation affects neural firing far beyond the stimulation site. This demonstrates the difficulty in predicting circuit-level effects of optogenetic manipulations and highlights the importance of closely monitoring neural activity in optogenetic experiments.

Dataset Information

Fully integrated silicon probes for high-density recording of neural activity.

Publications

Fully integrated silicon probes for high-density recording of neural activity.

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