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Why do these mice hallucinate? Scientists are in their heads

In a laboratory at the Stanford University School of Medicine, mice are seeing things. And it is not because they have been given drugs.

With the new laser technology, scientists have caused specific hallucinations in mice by turning on some neurons with light beams. The researchers reported the results Thursday in the journal Science.

The technique promises to provide clues about how the billions of neurons in the brain make sense of the environment. Eventually, research can also lead to new treatments for psychological disorders, including uncontrollable hallucinations.

"This is spectacular, this is the dream," said Lindsey Glickfeld, a neuroscientist at Duke University, who was not involved in the new study.

In the early 2000s, Dr. Karl Deisseroth, a psychiatrist and neuroscientist at Stanford, and other scientists designed neurons in the brains of living mice. to turn on when exposed to a flash of light. The technique is known as optogenetics.

In the first wave of these experiments, the researchers used light to learn how different types of neurons worked. But Dr. Deisseroth wanted to be able to detect any individual cell in the brain and turn it on and off with light.

So he and his colleagues designed a new device: instead of simply bathing a mouse's brain with light, it allowed researchers to emit small rays of red light that could attack dozens of individual brain neurons at once.

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To test this new system, Dr. Deisseroth and his colleagues focused on the brain's perception of the visual world. When light enters the eyes of a mouse or a human being, it activates nerve endings in the retina that send electrical impulses to the back of the brain.

There, in a region called the visual cortex, neurons quickly detect the edges and other patterns, which the brain then gathers into an image of reality.

The scientists inserted two genes into neurons in the visual cortices of mice. One gene made neurons sensitive to red laser light. The others caused the neurons to produce a green flash when activated, allowing researchers to track their activity in response to stimuli.

The designed mice were shown images on a monitor. Some were vertical stripes, others horizontal stripes. Sometimes the stripes were bright, sometimes blurred. The researchers trained the mice to lick a tube only if they saw vertical stripes. If they performed the test correctly, they were rewarded with a drop of water.

When the mice were shown images, thousands of neurons in their visual cortices turned green. A population of cells on in response to vertical stripes; Other neurons lit up when horizontal mice were shown.

The researchers selected a dozen neurons from each group to attack. Again they showed the stripes to the mice, and this time they also shot light at the neurons of the corresponding group. Connecting the correct neurons helped the mice to better recognize the fringes.

Then the researchers turned off the monitor, leaving the mice in the dark. Now scientists exchanged neurons for horizontal and vertical stripes, without rodents seeing anything. The mice responded by licking the pipe, as if they were actually seeing vertical stripes.

"It's not like a creature tells you: & # 39; Oh, wow, I saw a horizontal bar & # 39;" he said.

Dr. Churchland said more research would be needed to better understand why mice behaved as they did in response to flashes of red light. Did you see the horizontal stripes more clearly, or were you less distracted by deceptive signals?

One of the most notable results of the study came when Dr. Deisseroth and his colleagues reduced their beams of red light to fewer and fewer neurons. They continued to make the mice lick the pipe as if they were seeing the vertical stripes.

In the end, scientists discovered that they could trigger hallucinations by stimulating only two neurons. Thousands of other neurons in the visual cortex would follow the leadership of those two cells, blinking green when activated.

Dr. Deisseroth and his colleagues concluded that groups of neurons in the brain can tune in so that they are ready to fire even with a slight stimulus, like a snowbank prepared to become an avalanche.

But an elegant optogenetic device is not needed to make a few neurons activate. Even when they are not receiving a stimulus, neurons sometimes simply fire at random.

That poses a puzzle: if all you need are two neurons, why aren't we hallucinating all the time?

Maybe our brain wiring prevents it, said Dr. Deisseroth. When a neuron is fired at random, others can send a signal to calm down.

Dr. Glickfeld speculated that attention can be crucial to trigger the avalanche of neuronal action only at the right times. "Attention allows you to ignore much of the background activity," he said.

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