We have the technology!

January 10th, 2023

Written by: Joseph Stucynski

Understanding the brain may be one of the most complicated scientific problems in modern biology. Because the brain is so complex, sometimes scientists cannot easily answer questions about the brain using only the tools that currently exist. Developing new tools and research methods to address these more complicated questions about the brain poses significant engineering challenges. In fact, many labs and companies across the world are entirely dedicated to this task.

One new technology that is helping to revolutionize the way we study the brain is called Neuropixels. Neuropixels was developed for $5.5 million over a period of 5 years by the Janelia Research Campus, released in 2017, and is now used by hundreds of labs around the world.1

To understand what Neuropixels does, image a camera that you put on the end of a rope and lower it into the ocean. With your single camera down in the deep you can see the local environment and observe some fish nearby. But you are limited to the range of the camera at that depth. However, if you densely line the rope with hundreds of cameras, now you can observe the water environment along the entire length of the rope simultaneously and spot many more fish. With this information you can ask and answer new questions like ‘how do conditions at the bottom of the ocean affect conditions near the top?’, or ‘what happens when large currents sweep in and affect those different parts of the ocean?’.

This is the guiding philosophy behind the development of Neuropixels. The gold standard in understanding how a few individual neurons behave is to place an electrode at the tip of a probe (camera at the end of a rope, as per our ocean analogy) and lower it into the brain to record the neurons’ activity. This is very useful for understanding what these few neurons are doing in a small brain area, but you cannot see what is happening across the whole brain with this method.

The ability to record from individual neurons across large areas of the brain at the same time therefore represented an unsolved problem. Neuropixels addresses this by placing almost 1000 tiny electrodes along the entire length of its 1 centimeter long probe. When lowered into the brain, Neuropixels can record the activity of many hundreds of individual neurons in different regions of the brain simultaneously. This ability represents a giant leap forward from existing technology.

But why is this particularly useful for understanding what the brain is doing? To illustrate, let’s start with a question. When you are thirsty, how does your brain know when it’s time to drink and how much to drink? Some part of your brain needs to keep track of the water content in your body, which then must communicate to other parts of your brain that you need to find water when you’re thirsty. Upon finding the water you then need to consume the water, which requires muscle movements guided by motor neurons in another part of the brain. Even more neurons must keep track of how much you’re drinking to tell your brain to stop being thirsty.

Because this seemingly simple need is actually a complex constellation of behaviors, understanding what happens in the brain when you’re thirsty requires measuring what individual neurons do during that sequence of events, while also monitoring different parts of the brain.

In a paper from 2019, researchers at Stanford University proved the power of Neuropixels to get at this exact question. Previously it was known that several groups of neurons in an area of the brain called the hypothalamus keep track of thirst and water consumption, but it wasn’t known how those neurons might rapidly signal other parts of the brain during the act of consuming water.

The neuroscientists inserted Neuropixels in 4 distinct locations in the brain. This enabled them to record from thousands of individual neurons across the entire brain! They then presented thirsty mice with water and measured the neural activity patterns when the thirsty mice drank until they were satisfied. By combining the activity of up to 23,000 individual neurons across the brain they were able to gain a clearer understanding of how different parts of the brain work together to control drinking behavior across time.

Surprisingly, they found that when the mice licked the water it produced cascades of neural activity across the entire brain, even in areas that were not thought to be directly responsible for controlling thirst. In fact, the entire brain appeared to react to licking the water. Fundamental insights like this have the power to shift how we as scientists view the brain, and to inform future investigations.

Recently in 2022 Neuropixels probes have even been used in humans for the first time, helping neurosurgeons record from large neuron populations during surgery in patients with epilepsy!3 As neuroscientists ask increasingly complex questions, we must continually make use of cutting edge tools to meet these demands. Neuropixels technology and the efforts by scientists and engineers to develop it is a great example of this principle.

References

1.https://www.hhmi.org/news/neuropixels-technology-ready-for-release

2. Allen, W.E., Chen, M.Z., Pichamoorthy, N., Tien, R.H., Pachitariu, M., Luo, L., Deisseroth, K. Thirst regulates motivated behavior through modulation of brainwide neural population dynamics. Science, 2019.

3. Paulk, A.C., Kfir, Y., Khanna, A.R., Mustroph, M.L., Trautmann, E.M., Soper, D.J., Stavisky, S.D., Welkenhuysen, M., Dutta, B., Shenoy, K.V., Hochberg, L.R., Richardson, R.M., Williams, Z.M & Cash, S.S. Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex. Nature Neuroscience, 2022.

Image by Gerd Altmann from Pixabay

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