Challenges and opportunities for large-scale electrophysiology with Neuropixels probes

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Abstract

Electrophysiological methods are the gold standard in neuroscience because they reveal the activity of individual neurons at high temporal resolution and in arbitrary brain locations. Microelectrode arrays based on complementary metal-oxide semiconductor (CMOS) technology, such as Neuropixels probes, look set to transform these methods. Neuropixels probes provide ∼1000 recording sites on an extremely narrow shank, with on-board amplification, digitization, and multiplexing. They deliver low-noise recordings from hundreds of neurons, providing a step change in the type of data available to neuroscientists. Here we discuss the opportunities afforded by these probes for large-scale electrophysiology, the challenges associated with data processing and anatomical localization, and avenues for further improvements of the technology.

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

Matteo Carandini, James Jun, Nicholas Steinmetz … (2017)

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-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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Genetically encoded indicators of neuronal activity.

Michael Lin, Mark J. Schnitzer (2016)

Experimental efforts to understand how the brain represents, stores and processes information require high-fidelity recordings of multiple different forms of neural activity within functional circuits. Thus, creating improved technologies for large-scale recordings of neural activity in the live brain is a crucial goal in neuroscience. Over the past two decades, the combination of optical microscopy and genetically encoded fluorescent indicators has become a widespread means of recording neural activity in nonmammalian and mammalian nervous systems, transforming brain research in the process. In this review, we describe and assess different classes of fluorescent protein indicators of neural activity. We first discuss general considerations in optical imaging and then present salient characteristics of representative indicators. Our focus is on how indicator characteristics relate to their use in living animals and on likely areas of future progress.

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Selective gating of visual signals by microstimulation of frontal cortex.

Tirin Moore, Katherine M Armstrong (2003)

Several decades of psychophysical and neurophysiological studies have established that visual signals are enhanced at the locus of attention. What remains a mystery is the mechanism that initiates biases in the strength of visual representations. Recent evidence argues that, during spatial attention, these biases reflect nascent saccadic eye movement commands. We examined the functional interaction of saccade preparation and visual coding by electrically stimulating sites within the frontal eye fields (FEF) and measuring its effect on the activity of neurons in extrastriate visual cortex. Here we show that visual responses in area V4 could be enhanced after brief stimulation of retinotopically corresponding sites within the FEF using currents below that needed to evoke saccades. The magnitude of the enhancement depended on the effectiveness of receptive field stimuli as well as on the presence of competing stimuli outside the receptive field. Stimulation of non-corresponding FEF representations could suppress V4 responses. The results suggest that the gain of visual signals is modified according to the strength of spatially corresponding eye movement commands.

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Author and article information

Journal

Journal ID (nlm-ta): Curr Opin Neurobiol

Journal ID (iso-abbrev): Curr. Opin. Neurobiol

Title: Current Opinion in Neurobiology

Publisher: Current Biology

ISSN (Print): 0959-4388

ISSN (Electronic): 1873-6882

Publication date PMC-release: 1 June 2018

Publication date (Print): June 2018

Volume: 50

Pages: 92-100

Affiliations

[1 ]University College London, London, UK

[2 ]Allen Institute for Brain Science, Seattle, WA, United States

Article

Publisher ID: S0959-4388(17)30316-1

DOI: 10.1016/j.conb.2018.01.009

PMC ID: 5999351

PubMed ID: 29444488

SO-VID: 42f41c21-1fa9-40e7-9987-c79e52466a19

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Challenges and opportunities for large-scale electrophysiology with Neuropixels probes

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Abstract

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NeuroImaging Methods

Most cited references 61

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

Genetically encoded indicators of neuronal activity.

Selective gating of visual signals by microstimulation of frontal cortex.

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