How to make sense of the brain's billions of neurons

A unique global collaboration is attempting to transform the way we study the brain. If it succeeds, it could start to address longstanding unanswered questions about how brain disorders alter our neural circuits.

To even begin to understand the complexities of the brain we need to measure countless single neurons all over the brain at the same time. Until recently, no one thought that was possible.

Step forward neuropixel probes

Neuropixel probes are tiny, super-sensitive electrodes that can record the pulse of multiple single neurons from multiple brain regions and then digitise those signals.

neuropixel probe in close up

Credit: Mladen Barbic, Janelia

They are thinner than a human hair, each with 960 recording sites and 384 channels that produce high-definition, high-quality data about brain activity.

Tim Harris, senior fellow at the Janelia Research Campus at Howard Hughes Medical Institute, led a collaboration of brain scientists and engineers at the Janelia Research Center, the Allen Institute, UCL and imec, a nanoelectronics research centre, to create the probes.

The engineering had three phases:

Matteo Carandini led one of the UCL laboratories that tested the prototypes and contributed the code most other labs use to interpret the probes' output.

He says that the scientific challenge – how to record hundreds of individual neurons in many different regions of the mouse brain – was huge. But in one respect it was simple.

"The tool did not exist, so it had to be built. Sometimes it's necessary to seek new technologies, and to go beyond the confines of the laboratory."

Shared risk, shared benefits

The scale of the collaboration has been integral to the success of the project. It would have been a very risky project for a single laboratory. Collaboration has meant that not only are the work and benefits shared, but also the risk.

And collaboration also has huge scientific benefits. "Both within the lab and across labs, other people invariably come up with better solutions. In fact, often they already know the solutions," says Matteo. "All you need to do is ask them."

Watch Professors Anne Churchland and Matteo Carandini explain how the probes will record and share data in real time.

Releasing the first generation of probes

There is high demand for the neuropixel probes and to meet it the various partners in the collaboration have devised a method to produce the probes commercially at cost price.

The first generation of neuropixel probes will be released to scientists worldwide this summer.

Initially, the probes will be used on the brains of mice. A new project is being planned to produce a probe for recording in non-human primates.

It's likely that one day these kind of probes will be inserted into the brain of human patients, for example people who are completely paralysed and need to move robotic arms through the brain activity. This is still fairly far away. But ambitious research to finesse the next generation of probes is already underway.

"Neuropixels will advance the understanding of the function of individual brain regions, but most especially the coordinated activity of multiple brain regions."
Tim Harris, senior fellow, Janelia Research Campus

Collectively, the different labs can finally look at what is happening throughout an entire mouse brain and this could radically alter our existing knowledge about which brain regions are involved in different behaviours, and how brain disorders alter our neural circuits.

Virtual lab

Neuropixel probes will be used by the International Brain Lab, a 'virtual lab' that brings together 21 leading neuroscience groups from around the world. Neuroscientists will work together to understand a single behaviour in mice. This novel approach will allow greater insight into learning and decision making than any single lab could achieve alone.

The project is funded by the Simons Foundation and Wellcome.

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