Neurons recorded en masse

E D WA RD M. CA LL AWAY & AN UPAM K. G A R G

C

ountless videos depict neurons

communicating with one another, flashing on and off as they signal to their neighbours. But these videos are a fan-tasy, constructed to illustrate how we think that the brain might work. Real videos of neuronal populations at work in live brains lack either the spatial resolution or the temporal precision to infer functional interactions. On page 232, Jun et al.1 describe a silicon probe called Neuropixels, which can simultaneously record the activity of more than 200 individual neu-rons. This technology promises to have a major impact on neuroscience.

There have been intensive efforts to increase the speed, density and number of simultaneous recordings taken from single neurons. Devel-opments in optical approaches to measure activity have increased density and cell-count recordings 2, but such approaches cannot reliably identify the precise timing of spikes of neuronal activity, and recordings are typically limited to structures near the brain’s surface. By contrast, electrical recordings can resolve spikes from individual neurons with milli s econd pre-cision 2, and thin electrodes can penetrate deep into the brain with minimal damage. But taking dense electrical recordings is challenging. These challenges arise from the proper-ties of the brain itself. Neurons are tiny (their cell bodies are about 10 micrometres across) and densely packed (about 100,000 per cubic

millimetre in the brain’s cerebral cortex)3. To measure electrical activity accurately, elec-trodes must be placed very close to cell bodies, and must be designed such that spikes of activ-ity from different neurons are distinguishable from one another.

To meet these challenges, modern silicon-based probes contain arrays of closely spaced recording contacts. Each contact can pick up spikes from many neurons, and the spikes from any one neuron can be detected by multiple contacts 2,4 — the activity of individual neurons can then be dissected by comparing signals from each contact. This approach works best if contacts are densely packed. However, more contacts take up more space and require more wires. The devices become thicker and cause more damage when inserted, potentially killing the neurons they are intended to interrogate.Neuropixels represents a dramatic leap forward from previous probes. The advance was possible thanks to four non-profit fund-ing agencies, whose large financial commit-ment enabled neuroscientists and engineers to work together.

Jun et al. used next-generation silicon- fabrication techniques to produce a probe that has 960 recording contacts. These chan-nels are set roughly 20 μm apart, along a probe that has a cross-section of 70 μm × 20 μm and is 1 cm long, meaning that even the deepest structures of a mouse brain can be accessed (Fig. 1). Although silicon probes with a simi-lar contact density exist, they are limited to

far fewer channels (a typical probe might have 32 channels), and often require too many wires for chronic implantation. The on-probe electronics and wiring of Neuropixels can accommodate simultaneous recordings from 384 of its 960 channels, and the channels being measured can be switched. Switching offers the substantial benefit of allowing active recording sites to be altered after implantation, so that structures of interest can be selectively sampled.

The process began with a prototype design, test and redesign loop that systematically benchmarked materials, electronics and con-figurations to identify the best possible design for a laboratory probe. In early prototyping experiments, Jun et al. tested how the width of the probe affected tissue damage. Stand-ard probes in the field range in width from 50 μm to more than 200 μm, depending on the number and configuration of recording sites. The authors aimed to maximize the number of recording sites, while minimizing the size of the probe to decrease tissue damage. They found little difference in the number of neu-rons sampled per channel between probes 50 μm and 70 μm wide, suggesting that the wider probe causes negligible differences in tissue damage. They also showed that there was no disadvantage to using probes with switches.

At the same time, Jun and colleagues evaluated recording materials. The material typically used to make recording contacts

BRAIN TECHNOLOGY

Neurons recorded en masse

A silicon probe that is inserted into the mouse brain can precisely measure the activity of about 200 individual neurons simultaneously. This tool should improve our ability to study functional neuronal circuitry. See Letter p .232

Figure 1 | Probing brain activity with Neuropixels. a , A typical probe used to interrogate neuronal activity in rodent brains might be 100 μm wide, 0.8 mm long and take recordings of neuronal activity through 32 channels set about 50 μm apart, enabling simultaneous recording of about 20 neurons. Jun et al.1 have developed an improved probe called Neuropixels. Recording channels are set about 20 μm apart, along a probe that is 1 cm long and

70 μm wide. In total, there are 960 channels, from which sets of 384 channels can be selected for simultaneous use (red), choosing from several possible configurations of channels. b , The length of Neuropixels and its ability to switch channel configurations enables examination of several brain regions. The activity of about 200 individual neurons can be measured simultaneously.

172 | N A T U R E | V O L 551 | 9 N O V E M B E R 2017

NEWS & VIEWS

For News & Views online, go to https://www.sodocs.net/doc/2a12447732.html,/newsandviews

across both local and distant brain structures. In summary, the development of Neuropixels ushers in a new era of microelectrodes. The versatility of this technology opens the door

Colliding

shells

Scattering

200 AU

2,000 AU

Supernova

centre Radiation

ejected. Each shell contains material that has a range of speeds, with the fastest material on the outside. As the supernova expands (green arrows), the leading edge of one shell collides with the inner edge of a previously ejected shell, at a distance of about 200 au from the supernova centre. This produces radiation, some of which scatters off the surrounding material before ultimately escaping. Eventually, the star collapses to a black hole (not shown).

9N O V E M B E R2017|V O L551|N A T U R E|173