Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

Abstract

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

Electrode pooling: boosting the yield of extracellular recordings with switchable silicon probes

“…These new probes already offer substantial opportunities to pool electrodes. Indeed Steinmetz et al (2021) report an example of pooling two electrode banks, although their approach to unmixing the signals differs from that advocated here.…”

“…In most circumstances the user can probably use static selection to pick 40% of the electrodes and still monitor every possible neuron. By contrast, the recently announced Neuropixels 2.0 (Steinmetz et al, 2021) has an electrode:wire ratio of 13.3. Another device, currently in engineering test, will have 4416 sites on a single 45 mm shank, with electrode:wire ratio of 11.5.…”

“…If they drift too much, for example because the electrode array moves in the brain (Jun et al, 2017a), then a recalibration by another split-mode session may be in order (Figure 3A). Alternatively electrode drift may be corrected in real time if signals from neighboring electrodes are available (Steinmetz et al, 2021), a criterion that may flow into the selection of switches for pooling. Chronically implanted electrode arrays can record for months on end (Steinmetz et al, 2021), and the library of spike shapes can be updated continuously and scanned for new pooling opportunities.…”

“…To this end, the BRAIN Initiative has called for the development of technologies for recording “dynamic neuronal activity from complete neural networks, over long periods, in all areas of the brain”, ideally “monitoring all neurons in a circuit” (BRAIN Working Group, 2014). Recent advances in the design and manufacturing of silicon-based neural probes have answered this challenge with new devices that have thousands of recording sites (Jun et al, 2017b; Dimitriadis et al, 2018; Rios et al, 2016; Torfs et al, 2010; Steinmetz et al, 2021). Still, the best methods sample neural circuits very sparsely, for example recording fewer than 10 4 cells in a mouse brain that has 10 8 (Stevenson, 2013).…”

“…Because there is no local amplification or dynamic switching, the issues of heat dissipation or photosensitivity do not arise. This method has been incorporated recently into flat electrode arrays (Müller et al, 2015) as well as silicon prongs (Jun et al, 2017b; Lopez et al, 2017; Steinmetz et al, 2021). It allows the user to choose one of many electrodes intelligently, for example because it carries a strong signal from a neuron of interest.…”