Crazy mouse vision research experiment

When Cris Niell said he wanted to study how mice look at things, they are not recognized by more advanced neuroscientists. Mice are nocturnal animals, they navigate their noses and beards, so many researchers believe that many visual experiments on mice are meaningless. Often, researchers use monkeys as an alternative model because monkeys have a field of view that is directly in front and a more acute vision than mice. More importantly, scientists can rely on decades of proven technology to apply the results of primate experiments to the human visual system. “People say it’s crazy to study the visual system in old mice,” recalls Niell.

But he has always believed that these rodents can bring something unique to the study of the visual system. Since the 1960s, researchers have used cats and monkeys to do some research and found important clues that the brain maps information from the eye to consciousness. But to do more in-depth research at the cellular level, researchers must be able to control and monitor neurons, which is difficult to do in complex systems of cats and monkeys, and is much easier in mice. If the process of treating visual stimuli in mice is similar to that of primates, we can figure out how the brain extracts information from large amounts of data after being stimulated externally—and even figuring out how the brain works.

While many neuroscientists questioned Niell's ideas, he found a supporter, Michael Stryker of the University of California, San Francisco. Stryker provided Niell with the opportunity to pursue a postdoctoral fellowship in his lab, and the two began preparing for this crazy mouse vision experiment in 2005.

Nearly ten years later, the two researchers have more research colleagues. At the annual meeting of the Neuroscience Society held last year, Niell attended many seminars on mouse vision. In March 2012, Seattle's Allen Institute of Brain Science announced a 10-year research project that spent more than $100 million to study the mapping of mouse vision on the brain. In June of this year, a two-week training course at the Cold Spring Harbor Laboratory in New York showed the future and focus of mouse vision research. Andrew Huberman, a neuroscientist at the University of California and director of the program at the University of California, said that more than three-quarters of the 22 students chose to investigate how to use mice for visual system research. In addition, he also said that in the first year of 2001, only one or two students chose to study in this field, but now the number of students has increased exponentially. "This is an explosive growth."

Much of the focus is due to advances in technology, using optogenetics to enable researchers to monitor and control specific mouse neurons. Low cost and no ethical restrictions are also attractive places for this project.

Huberman points out that for now, whether they can reveal useful information about human vision is still an open question. “The neuroscience of the mouse visual cortex is like a smart phone. Everyone thinks they need to buy a play, but whether the smartphone is just a convenience, or a distracting toy, or There is a great invention after the invention of electricity, and it still needs time to verify."

Rodent attraction

Niell wants to revisit some well-known and groundbreaking visual science experiments. In the 1950s and 1960s, David Hubel and Torsten Wiesel placed electrodes on the back of the brains of cats and monkeys, using speakers to track neuronal activity. When the animals saw slashes and moving dots, the researchers monitored their brain activity. The results they are monitoring show that the neuron tissue area corresponds to motion and edge graphics. This discovery earned them a Nobel Prize.

It turns out that neurons filter the information that the eye inputs into the visual cortex: some neurons respond only to vertical lines, some response horizontal lines, some response slashes, and some corresponding moving origins, and so on.

Niell now manages a laboratory at the University of Oregon Eugene, and he knows that it is not easy to apply the findings to mice. For example, electrodes placed in the brain of mice may damage the brains of fragile mice, not only failing to monitor, but also affecting the activity of the mice themselves. But in a subsequent study, they redesigned the research equipment, and Niell and Stryker now use mouse microprobes to record mouse brain activity.

In response to a series of slanted neuron maps, neuronal activity peaks at a particular graphical orientation. But when the preferred oblique angle of the oblique line becomes other angles, these cells are silent. Stryker recalls, “I can't believe these images are so clear, like the charts on books.” Stryker and Niell consider this to be a strong evidence that mice can be used as visual research models for higher animals.

When the results of this study were spread, their labs soon had visitors. The earliest were the two neuroscientists at the University of California, Hillel Adesnik and Bassam Atallah. Adesnik and Atallah have been working on the connection of mouse brain slices. They want to test how cells respond to stimuli in new cutting tissues, but there are no mature treatment techniques. So when they heard the news from San Francisco, they immediately jumped onto the motorcycle for 800 kilometers to learn from Niell. Since that visit, experiments conducted by Adesnik and Atallah have confirmed the interaction of neurons in the visual cortex of mice.

But Edward Callaway, a neurobiologist at the Salk Institute, points out that it is not yet known how far the science can go. "So far, we haven't found anything new from the mouse visual system. But this Not surprising, because it took us 40 years to study the monkey vision system."

But these early data have led researchers to take a big step toward using simple models to reveal the goals of complex brain activity. For example, the results of this study indicate that the mouse brain has a complex process similar to that of primates.

Coincidentally, at about the same time, Matteo Carandini of the University of London turned his research horizons from monkeys and cats to mice. He wants to study the activity of the upstream and downstream of the neural circuit, so he must record the activity of a single neuron. This is very difficult to do in the complex brain system of monkeys and cats, so Carandini began to explore the neuronal activity of model mice.

He and his team developed a task: training the mouse to press a button while seeing the stripes. The team also monitors the visual processing of mice as they move or explore virtual environments. Now Carandini wants to manipulate specific neurons under such experimental conditions to observe changes in mouse behavior. He believes that research on small, flat brains in mice can map the behavior of brains in higher animals.

Blurred vision

But Carandini and many researchers in this field have acknowledged that this study has some limitations. For example, no one can deny that the mouse's vision is not so good; Niell estimates that their vision is equivalent to 1/100 of human vision (equivalent to the blind). Therefore, some research tasks cannot be completed in rodents. “We wanted to use primates to get the right results,” says WHO researcher Callaway.

However, it has also been said that the similarities between mice and humans are greater than differences. The visual cortex of mice contains the same neural types, the same species ratios, and the same mechanism of action as humans. In evolutionary relationships, mice are closer to humans than cats. In fact, the brain regions of mice are easier to handle than monkeys and cats.

Not all scientists agree with this statement. Because the difference between the mouse and the monkey's brain is very obvious. The first is size, followed by the number of neurons. Some people think that the brain of a mouse is too small to be studied in the same way.