Simultaneously spy on thousands of neurons in the brain’s vision center



Neurons in eight areas of the brain work together to process visual information. Researchers have now documented the activity of these neurons at a magnitude and resolution never before reported.

The scientists followed the reaction of individual neurons (white dots) through the mouse’s visual center when the animals saw an image on a screen. This allowed the team to trace the sequence of events triggered when the eyes detect an important sight. Credit: S. Ebrahimi et al./Nature 2022

Using a custom-designed microscope to peer into the mouse brain, the scientists tracked the activity of single neurons throughout the visual cortex.

These recordings, made within tenths of a second after the animals have seen a signal on a screen, expose the complex dynamics involved in understanding what the eyes see. In an unprecedented combination of breadth and detail, the results describe the behavior of more than 21,000 total neurons in six mice over five days, the team of Howard Hughes Medical Institute researcher Mark Schnitzer reports in the journal Nature May 18, 2022.

His team is the first to gain insight into the activity of individual cells occurring at the same time in eight parts of the brain involved in vision. “People have studied these areas of the brain before, but previous imaging studies didn’t have cellular resolution across the entire visual cortex,” says Schnitzer, a neuroscientist at Stanford University.

The work highlights the dramatic sequence of events that take place in the brain from the moment it receives messages from the eyes until it decides how to react to that sight. The researchers’ thorough but fine-grained imaging approach allowed them to collect an “incredible” set of data, says Tatiana Engela computational neuroscientist at Cold Spring Harbor Laboratory who was not involved in the study.

“It’s fascinating to see everything the brain is doing in the moments immediately following the sight of the stimulus through the eyes.”

Mark Schnitzer, HHMI researcher at Stanford University

While previous studies have already explored aspects of this process, such as variations in the activity of single neurons and coordination between larger brain areas, this research offers a new, broader view, she says. “The scale at which they are able to address these topics is very impressive.”

When the eyes see an image, they send out electrical signals that end up in the visual cortex, the wrinkled outer layer of the brain near the back of the head. There, the signals trigger a flurry of activity as neurons work together to register an image, evaluate it, and decide how to respond to it.

To capture activity through the visual cortex, Schnitzer and his colleagues built a custom microscope with a wide field of view. Their system could also capture detail at a resolution of a few thousandths of a millimeter, small enough to detect single neurons. Using genetically modified mice with neurons that fluoresce when sending signals, the team was able to observe the activity of these cells.

During the team’s experiments, mice had to make a choice based on one of two visual cues. One prompted the animals to lick a spout for sugar water, the other cue indicated “do not lick”. The mice performed several of these tests for five days.

With recordings made from the brains of mice, the team asked a simple question: what happens in the brain when we see something? Their results expose this invisible process to a temporal resolution of fractions of a second and reveal surprising nuances.

Scientists, for example, already knew that individual neurons behave variably when responding to visual signals transmitted by the eyes. But Schnitzer’s team’s experiments revealed a pattern of this unreliable behavior. This model could allow areas of the brain receiving signals from neurons to understand them and accurately interpret the visual scene.

The researchers also documented how, around 200 milliseconds after the visual cue appeared, the animals switched mental gears: the messages from the eyes caused a massive rearrangement in the activity of different brain areas. About 500 milliseconds later, this surge subsided and the activity became more stable and recognizable. Then, about 600 milliseconds later, another signal appeared, activating all eight areas of the brain. This signal encoded the animal’s decision to remain motionless or to fetch sugar water. The researchers learned to read the signal, so they could predict what response the mouse would make.

“It’s fascinating to see everything the brain is doing in the moments immediately after the eyes perceive the stimulus,” says Schnitzer.



Sadegh Ebrahimi et al. “Emerging Reliability in Sensory Cortical Coding and Cross-Area Communication.”Nature. Published online May 18, 2022. doi: 10.1038/s41586-022-04724-y


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