【Animal Modeling】-Researchers used thin light beams to reorganize mouse brain cell network

  A new study in the Science magazine shows that neurons fired at the same time are really connected in series, which shows that the "three-pound computer" on our heads may be more malleable than we thought.

  In the latest issue of Science, neuroscientists at Columbia University proved that if only one neuron in the neural network is stimulated, then a group of neurons that can be simultaneously stimulated will be reactivated almost a day later. Their research results indicate that the reactivated neuron groups may form the basic building blocks of learning and memory, but further research is needed. The original hypothesis was put forward by psychologist Donald Hebb in the 1940s.

  Dr. Rafael Yuste, a professor of neuroscience at Columbia University and the corresponding author of this study, said: "I always thought that the brain is immutable. But then I saw this result and exclaimed:'Gosh, the brain is completely plastic.' We are dealing with a plastic computer that is constantly learning and changing."

  Researchers control and observe the brain of a living mouse by applying the optogenetic technology that has completely changed the field of neuroscience in the last ten years. They injected a virus containing a light-sensitive protein into the mouse so that the light-sensitive protein can Mark on specific brain cells. Once the light-sensitive protein enters the cell, researchers can rely on the light-sensitive protein to activate neurons remotely with light, just like switching programs on TV.

  The mouse can run freely on the treadmill, but its head is always under the microscope. By firing a beam of laser light, the researchers passed the laser light through the mouse brain to stimulate a small group of cells in the visual cortex. Then they fired a second laser, and when the neurons were excited, they recorded the increase in calcium levels when each neuron was excited, thereby obtaining a single cell's activity imaging.

  Before the discovery of optogenetics, scientists had to open the brains of mice, then implant electrodes in the living tissues, and record their responses by activating the tissues with electrical punctures. However, even the mouse brain tissue containing 100 million neuronal cells, which is only one thousandth of our humans, is too dense to observe the neuronal response carefully.

  The emergence of optogenetics allows researchers to access the mouse brain non-invasively and control it more accurately. In the past decade, researchers have restored vision and hearing in blind and deaf mice by manipulating specific areas of the mouse brain, and made normal mice more aggressive.

  This breakthrough study that allows researchers to reorganize cell clusters in the brain is the culmination of more than a decade of work.

  Through the study of tissue samples from the visual cortex of mice, Yuste and his colleagues discovered that nerve cells can coordinate their stimulus responses in a tiny network called the nervous system, which was published in the 2003 issue of Nature.

  One year later, they showed that the nervous system is stimulated through a temporal pattern.

  With the continuous advancement of the technology of controlling and observing cells in vivo, they have learned that these nervous systems are active even in the absence of stimulation. They used this information to develop mathematical algorithms for finding the nervous system in the visual cortex. When they studied early tissue samples, they found that the nervous system in living animals can also be stimulated one by one in a sequence pattern.

  Current research in Science magazine shows that these neural networks can be artificially implanted and replayed, just like a Madeleine cake soaked in tea, prompting novelist Marcel Proust to recall his childhood memories, Yuste said.

  The combination of

  two-photon calcium imaging and two-photon excitation technology allows researchers to record the response of individual cells to light stimulation. Although previous studies have also used single cells as research targets and recorded individual cell responses, no one has shown that a bunch of neurons in the brains of living animals can fire at the same time to mark their so-called "neural microcircuits."

  As a member of the American Institute of Data Science, Yuste said: "If you told me a year ago: we could stimulate 20 neurons out of 100 million neurons in the mouse brain and change their behavior, I would say, We can't do it." "Because it is as difficult as rearranging three grains of sand on the beach."

  Researchers believe that their artificially activated neuron network may implant a completely unfamiliar image into the brain of mice. Now they are developing a behavioral study of mice to try and prove this conjecture.

  The lead author of the study, a postdoctoral researcher at Columbia University, Luis Carrillo-Reid, said: "We believe that these methods of reading and writing activities into the living brain will have a significant impact in the fields of medicine and neuroscience. "

  Professor of psychiatry at Columbia University Medical Center, Dr. Daniel Javitt was not involved in the study. He said: This work may be used to restore the normal connection patterns of the brains of people with epilepsy and other brain disorders. However, before optogenetic technology can be applied to the human body, major technical obstacles need to be overcome.

  This research is part of a $300 million brain mapping effort, also known as the "American Brain Initiative." The predecessor of the project came from an early proposal by Yuste and his colleagues, which was developed for mapping fruit flies. A tool for brain activity and used in more complex mammals, including humans.