Using high-resolution Neuropixels silicon probes thinner than a human hair, scientists at the Allen Institute for Brain Science have captured hundreds of split-second electrical signals that fire when an animal is interpreting what it sees. Analyzing the data collected reveals that functional connectivity between different areas mirrors the complex structural hierarchy in the visual system and provides key insights on how signals propagate along the organizational layers of the visual system.

Electrical probes
High-resolution Neuropixels silicon probes. [Allen Institue]

“Historically, people have studied one brain region at a time, but the brain doesn’t mediate behavior and cognition with just one area alone,” says Shawn Olsen, PhD, Associate Investigator. “We’re learning that the brain operates through the interaction of areas and signals sent from one area to another, but technical limitations have prevented us from studying this in depth in the past. We really needed the integrated view that this dataset provides to start to understand how that works.”

This new large-scale study of simultaneous recording across numerous areas in the brain’s visual system is published in Nature in an article titled, “Survey of spiking in the mouse visual system reveals functional hierarchy.”

“At a very high level, we want to understand why we need to have multiple visual areas in our brain in the first place,” said Josh Siegle, PhD, Assistant Investigator in the Allen Institute’s MindScope Program. “How are each of these areas specialized, and then how do they communicate with each other and synchronize their activity to effectively guide your interactions with the world?”

Allen Institute researchers prepare for a Neuropixels experiment. L to R: Researchers Josh Siegle, Tamina Ramirez, Gregg Heller and Severine Durand. [Allen Institute]

Siegle and other MindScope researchers including Olsen, Xiaoxuan Jia, PhD, Senior Scientist, and Christof Koch, PhD, Chief Scientist, led a team of researchers to build a public database of electrical spikes from approximately 100,000 neurons in the mouse brain—the largest collection of neural electrical activity recordings in the world. Each experiment in the database captures information from hundreds of brain cells from up to eight different visual regions of the brain at once which allows scientists to trace visual signals in real-time as they move from the animal’s eyes to visual processing regions in its brain.

Visual information travels along the anatomical hierarchy through the brain, in which lower areas decipher simpler visual concepts like light and dark, while higher areas capture more complex ideas, like the shape of objects, the authors note.

The Neuropixels study builds on a previous study that used the Allen Mouse Brain Connectivity Atlas to map the physical connections in the mouse brain made by bundles of axons between many different areas of the brain and traced thousands of connections within and between the thalamus and cortex.

“If the connectivity data is like the brain’s road map, the Neuropixels dataset is akin to tracking traffic patterns in the brain,” says Koch.

Although signals in the brain move in a split second from one region to the next, the probes are sensitive enough to detect very slight time delays. These let scientists trace a real-time map of the route visual information takes in the brain. Comparing the functional and structural data, the researchers get a clearer picture of how information moves along neural paths.

“It’s as if we’re trying to map how cities are connected by watching the movement of cars on the road,” Koch said. “If we see a car in Seattle and then a few hours later we see that same car in Spokane and then much later we see the car in Minneapolis, then we have an idea that the connection from Seattle to Minneapolis has to pass through Spokane on the way.”

Just knowing the physical map isn’t enough to predict the functional flow of visual information. There are many different, redundant connections between two brain areas, even two neighboring areas. And like our system of interstate highways, arterial roads, and smaller roads, the brain has connections that are frequently used and those less travelled.

In addition to time delays of signals arriving at different locations in the brain that the researchers used to map functional connectivity, they used other measures such as the size of visual field each neuron responds to, to confirm functional hierarchy. Cells lower in the hierarchy are tuned to smaller portions of the animal’s visual world, while higher-level neurons react to larger regions of visual space.

The scientists captured simultaneous multipoint neural activity with mice engaged in viewing single or multiple images, or with mice rewarded to respond to a change in images with a lick at a waterspout. Information travels in the brain across the same hierarchical path in both situations, the authors observe.

When mice are trained to respond to a visual change, their visual neurons also alter their activity, and those cells higher in the hierarchy show even larger changes. Looking at the neural activity it is possible for scientists to predict if particular animal had successfully detected a change in the image.

When the mice received no visual input many of the same visual neurons still fired, albeit more slowly, but the order of information flow was lost. This may mean that the hierarchy is needed to process visual information, but the animals use the same cells for other purposes in a different circuit, the authors note.

“We know that our ability to create coherent representations of objects we are seeing is a critical process for survival. Our brains have actually designated around 30 to 50% of the cortex just for visual processing,” Jia said. “Our study suggests that this hierarchical processing of visual information is also meaningful or important for the animal.”

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