Li Ying: Uncover the other side of the brain "sweeper"
Li Ying in the laboratory Photo courtesy of Li Ying
In nature, most mammals can process all kinds of social information and produce social behaviors such as mating, fighting, parenting, predation, and flight.
How does the brain encode all kinds of social information?
This is the answer Li Ying is looking for.
When she saw Li Ying, she was on crutches.
Some time ago, she injured her knee playing badminton and had just finished the operation.
Although it is inconvenient to move, on weekdays, she drove more than ten kilometers to work at the Beijing Brain Science and Brain-like Research Center on Science Park Road, Changping District, Beijing, where her laboratory and doctoral students are located. Of course, there are still many problems waiting for her to challenge.
In nature, most mammals can process all kinds of social information and produce social behaviors such as mating, fighting, parenting, predation, and flight.
How does the brain encode all kinds of social information?
This is the answer Li Ying is looking for.
The journey of finding is uneven, there will be difficulties, and there will be falls, but Li Ying is not afraid.
"I hate the word'distress', because'disturbance' is like getting entangled in something and wanting to get rid of it. I prefer the word'challenge'. It is very positive and all difficulties can be overcome." , Li Ying told a reporter from Science and Technology Daily.
"Love at first sight" for the brain
In September 2003, Li Ying became an undergraduate in the School of Life Sciences, Nanjing University.
At that time, most of Li Ying's classmates chose botany, zoology, etc., but she chose a relatively small group of physiology.
In the first neuroanatomy class, Li Ying saw a brain slice for the first time and was deeply attracted by it.
The brain is divided into left and right hemispheres. There are many concave grooves on their surface, and there are raised backs between the grooves.
Looking at the brain slices in front of her, Li Ying sighed: "Beautiful! As charming as a maze."
Not only the structure, but also the color of the brain fascinated the 18-year-old Li Ying.
"Without staining, the gray matter is really gray, the white matter is also white, and the black matter is dark... These names are really interesting," she said.
What surprised Li Ying most was the close relationship between these parts of the brain and human consciousness, emotions, and behavior.
"I was thinking, why does the brain think?" she recalled.
Curiosity was ignited, and Li Ying plunged into the ocean of neurobiology.
In the summer of her junior year, she came to the Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences for an internship.
"The atmosphere there is very free. For the first time, I felt what it is to do scientific research." Li Ying said.
In order to complete her undergraduate graduation project, Li Ying came again to the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences in 2006, and studied with Du Jiulin, a researcher of the institute.
In Du Jiulin's memory, Li Ying was courageous.
"Most people prefer to do less risky research, or follow what others have done. This is easy to produce results, but lacks originality and pioneering. But Li Ying is not. She is very courageous and is not afraid of the unknown. When my undergraduate came to my laboratory for a summer internship, I wanted to keep her.” Du Jiulin said.
Easy to master difficult technology
In 2007, Li Ying became Du Jiulin's "disciple".
At that time, Du Jiulin's team was using zebrafish as a model animal to conduct research on neurological functions.
The zebrafish are 3 cm to 4 cm long and are covered with dark blue vertical stripes. When swimming in groups, they resemble galloping zebras.
In the early days, zebrafish were mainly used in the field of developmental biology research, but rarely in the field of brain function research.
However, in neurological research, zebrafish has two outstanding advantages as a model animal: one is that the juvenile fish is transparent and can be injected with fluorescent dyes or genetically modified methods to observe its nervous system activity in real time through imaging; the other is that it can be awake Of zebrafish, using electrophysiological technology to record the electrical activity of zebrafish neurons.
The diameter of neuronal cells in mice is about 5 microns, and the diameter of electrodes is about 1 micron.
Under the microscope, the electrode tip is used to attract the cell, and then form a whole-cell record, which is the basic function of electrophysiological technology.
The zebrafish neuron cell volume is about 1/50 of the mouse neuron cell volume, which is very difficult to operate.
It is great to be able to suck the cells cleanly, and it is even more difficult to maintain a stable state for a long time.
At present, not many people in the world can master this technology, but Li Ying quickly learned it at that time.
After solving this problem, Li Ying rushed to the next one.
Microglia are known as "scavengers" in the brain and are immune cells in the central nervous system.
In addition to immune function, do microglia have physiological functions?
Li Ying plunged into this uninterested subject.
This subject is like a cloud of fog, unable to see where to go, but the bold Li Ying bravely set off.
She wants to do what no one does, and she firmly believes that as long as she uses the right method, there will be a breakthrough.
After countless attempts, Li Ying discovered that microglia not only have immune functions, but also have physiological functions that regulate neural interaction.
However, the research results have not been published.
After being rejected again and again, Li Ying thought about giving up.
She asks for leave from her mentor and travels alone.
After a short break, Li Ying continued to refine the data and repeatedly modify the article.
In December 2012, related research results were published in the journal Developmental Cell, and the relevant content has now been cited more than 300 times.
In September this year, a study published in the journal Nature was based on the results of Li Ying eight years ago.
"This matter made me understand what it means to solve a problem and what it means to persist." Li Ying recalled.
Adjust the research focus and start again
The joy of publishing an article did not last long, because Li Ying's interest was not here.
"I am still more interested in how creatures produce thoughts, emotions, and behaviors. I want to know how biological nerves work when they are freely active?" she said.
At an academic conference, Professor Mark Schnitzer of Stanford University shared a technology-wearing a small microscope weighing about 2 grams on the head of a mouse, you can directly see the neural activity of the mouse in the state of free movement !
This aroused Li Ying's great interest. After the report, she asked Mark Schnitzer many questions.
Questions are growing, and opportunities come quietly.
At an academic conference, Li Ying met Professor Katrine Dillack, a member of the American Academy of Sciences and the chair of the Department of Molecular and Biology at Harvard University.
Li Ying nominated herself and wanted to join Katrine Dillac's laboratory team to study biological social behavior.
During the interview with Katrine Dirac, Li Ying mentioned the content of her interview with Mark Schnitzer.
Unexpectedly, Katrin Dirac also knew Mark Schnitzer, and this conversation turned out to be the beginning of the three-person collaboration.
In 2013, Li Ying joined the team of Katrine Dillack in the Department of Molecular and Biology at Harvard University.
However, before officially launching the research, she went to Marc Schnitzer's laboratory to learn head-mounted microscope imaging technology and learn how to perform surgery on deep brain regions of mice.
About 2 months later, Li Ying returned to Harvard University.
In the animal room in the basement, 26-year-old Li Ying used about 15 square meters of space to build her own independent experimental platform.
When a mouse moves freely, how does its socially-related brain area work?
In order to clarify this problem, Li Ying inserted a cylindrical lens with a diameter of about 0.85 mm into the brain area of the mouse about 5 mm deep, and then put on a microscope weighing about 2 grams for the mouse to observe the small body directly through the microscope. Working condition of mouse brain area.
Li Ying is impatient, and she feels that her efficiency is low if she doesn't produce anything for a few days.
The lens was inserted too far, the insertion position was wrong, the mouse died... the operation failed many times.
During that time, Li Ying was lonely, and she was accompanied by self-encouragement and firm belief.
"At that time, no one in the world had ever done it successfully. Our success rate could reach 10%, which was a leap forward." She said.
It took more than two years. After performing operations on hundreds of mice, Li Ying used head-mounted miniature microscope imaging technology for the first time to record in freely moving mice an important brain area that affects animal instinctive social behavior-the inner almond Nuclear calcium signal.
In addition, she also found that the neuropeptide oxytocin played a key role in distinguishing male and female information in male mice, but had no significant effect on female mice in distinguishing different social information.
Just when others thought that Li Ying would go down this road, she chose to change the track and start again.
In 2019, Li Ying returned to China and entered the Beijing Brain Science and Brain-like Research Center. She adjusted her research focus again.
"She is fearless and likes to challenge. Only in difficult subjects can she find her self-worth." Du Jiulin said.
For more than 10 years, in Du Jiulin's laboratory, there is still the championship trophy that Li Ying won in the badminton competition.
"She is very good. Playing badminton can kill boys." Du Jiulin told reporters.
(Intern reporter Dai Xiaopei)