Challenges and opportunities for large-scale electrophysiology with Neuropixels probes

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.

Figure 1

Growth of electrode technology leading to Neuropixels. (a) Sites per shank over time for a selection of devices. Devices without successful in vivo demonstrations are excluded. Blue, devices made from wires, refs [1, 3, 5, 7]. Red, passive silicon, refs [11, 12, 13, 14, 15, 16, 17, 18, 19]. Black, active silicon, refs [15, 20••, 21•, 22] (square icon indicates Neuropixels). (b)–(d) The Neuropixels probe. (b) Schematic of tip, showing sites arranged in dense checkerboard pattern. (c) The printed CMOS element, including the shank as well as circuitry implementing amplification, multiplexing, and digitization. (d) The packaged device, with flex cable and headstage for interfacing and further multiplexing. (e) Neuropixels probes on CMOS wafer. Panels (b and d) are reprinted with permission from Ref. [20^••].

Figure 2

Neuropixels penetrations through the brain. (a) Example recording vectors that can be achieved with single Neuropixels probes. Left, Oblique sections through a reference brain atlas with hypothetical probe tracks illustrated in white. Right, Locations of the sections (red) shown at left. VISp, primary visual cortex; LGd, dorsal lateral geniculate nucleus; MOp, primary motor cortex; CP, caudoputamen; PL, prelimbic cortex; BLA, basolateral amygdala. All scale bars 1 mm. The Allen Institute Common Coordinate Framework reference atlas was used to generate these images. (b) Histological reconstruction of an actual probe track, showing DAPI stain (blue) without (top) and with (bottom) overlay of the fluorescent indicator DiI (orange) used to coat the probe. Due to small shank dimensions (70 × 20 μm), Neuropixels probes must be localized with a dye or with functional signatures. (c) Example LFP recording and features that can be used to localize probe sites. Left, sample of raw LFP signal from a subset of channels with sharp-wave ripple indicated (red arrow) and zoomed-in (insert). Right, total LFP power averaged over the recording, showing peak in dentate gyrus. Panel c is reprinted with permission from Ref. [20^••].