Text | Bu Jinting
Before the age of 18, Yang Wannan never thought that she would become a scientist. The reason is that she has loved philosophy since she was a child, and she studied liberal arts in high school, and none of her parents are engaged in jobs related to science.
After graduating from high school, Yang Wannan came to the University of Edinburgh in the United Kingdom to study biology; in her junior year, she became interested in neuroscience and won the opportunity to do experiments in the neuroscience laboratory of the Massachusetts Institute of Technology (MIT) in the United States; after her junior year, she successfully switched from biology to neuroscience; and now, this "post-95" girl, who used to be a liberal arts student, came to the laboratory of György Buzsáki, a professor in the Department of Neuroscience at New York University School of Medicine, to study for a doctorate in neuroscience.
Yang Wannan studied at the University of Edinburgh in the United Kingdom as an undergraduate.
From liberal arts to biology to neuroscience, Yang Wannan's study and research experience has reached an amazing level. Recently, Yang Wannan published a paper in Science as the first author, revealing the physiological mechanism of selective memory in the brain. It is worth mentioning that this is the first time that Yang Wannan, a fourth-year Ph.D., has published an article as the first author.
"Now, I want to work hard all my life to study memory and hopefully become a good scientist. Yang Wannan said.
From liberal arts to neuroscience
In September last year, Yang Wannan submitted his paper to the journal Science, and it was accepted in February this year. They only went through one round of revisions, and it went quite well.
For Yang Wannan, the harvest is far more than just a Science paper. "In the first three years of my Ph.D., I often doubted myself and wondered if I could do good research, after all, I had been a liberal arts student before. Now, I have more confidence and confidence to devote myself to scientific research. She said.
When she was a child, Yang Wannan's favorite story before going to bed was "Sophie's World". Because of her love for philosophy, she naturally chose liberal arts in middle school. In this thinking mind, there are always some special questions: "How does the brain perceive the world, and what is memory?"
After graduating from high school, with the original intention of continuing to explore the "brain" and "memory", Yang Wannan came to the University of Edinburgh to study biology. However, in the face of a clueless major, an unfamiliar language environment, and a weaker foundation than most of her classmates, Yang Wannan once fell into a collapse and cried countless times.
In the summer of her sophomore year, Yang Wannan traveled to Japan, during which she happened to attend a lecture on neuroscience. The speaker's use of scientific and concrete methods to study and dissect the abstract issue of memory made her "hate to see each other late". "I fell in love with neuroscience right away. Before that, I had been looking and seeking, and now I have a clear direction and goal. Yang Wannan said.
With a spirit of refusal to admit defeat, Yang Wannan switched to neuroscience courses when she went to the University of California, Los Angeles (UCLA) for exchange in her junior year.
Yang Wannan exchanged at UCLA.
At that time, the one-year exchange period was coming to an end, but Yang Wannan was well aware of the gap between herself and other science and engineering students, and in order to win the opportunity to do research in other laboratories in the United States, she sent emails to all interested professors, but thousands of emails were lost. It just so happened that a professor of neuroscience at MIT came to UCLA to give a lecture, and Yang Wannan asked a lot of questions, and after the lecture, Yang Wannan sent dozens of emails asking about the laboratory.
Perhaps it was the sincerity that moved the professor, and Yang Wannan really won this opportunity. Interestingly, Sun Chen, a Ph.D. in neuroscience that Yang Wannan met at MIT, later became her husband and was also the second author of this paper. "After getting to know him, studying the brain and memory became our common obsession. "They both have a love of philosophy and a passion for neuroscience.
Yang Wannan and her husband Sun Chen.
After returning to the University of Edinburgh at the end of her junior year, Yang Wannan successfully changed her major. After graduating from her undergraduate degree, she moved to the lab of Buzsáki, a neuroscientist at New York University. Since then, Yang Wannan has finally been able to devote himself to exploring the mysteries of brain memory.
The Mystery of Selective Memory Consolidation
The hard work paid off, and Yang Wannan's first paper was listed in Science.
We know that the hippocampus is the most central part of the human brain that controls memory, so named because of its resemblance to a seahorse. Among them, rapid bursts of synchronized neuronal activity caused by the hippocampus produce sharp ripples during non-REM sleep and quiet wakefulness.
Sharp wave ripples are mainly composed of sharp waves, which are large negative waveforms, which were first observed in the hippocampal sub-region CA1 of rodents, and ripples, which are rapid and short-lived neural oscillatory activities, caused by highly synchronized neuronal activity, and ripples, whose waveform is similar to ripples stirred on the water surface.
So, when do hippocampal sharp ripples appear? After we notice something, the brain usually switches to an "idle" reevaluation mode, and the longest idle period usually occurs during sleep.
Buzsáki and colleagues have previously confirmed that when we actively explore sensory information or movement, there are no sharp ripples, and only during idle pauses.
Past studies have found that sharp ripples play an important role in the consolidation of memories. However, how does our brain mark which memories are important to make them permanent?
During her Ph.D., Yang replicated some classic neuroscience experiments, and she found that "location cells" have different activation characteristics at different stages of events, rather than being as static as described in textbooks. Importantly, there is a subset of sharp ripples that are made up of "location cells" in the hippocampus firing in a specific order. Location cells are called "GPS in the brain" and can encode the spatial location of the animal.
Yang Wannan had a flash of inspiration: "So, is it possible to use the characteristics of the location cells to determine the order of event development?" So, the research team began to record the behavior trajectory and neuronal activity of the mice as they continuously passed through the maze. When the rats drank water and ate food after a pause in the maze, they recorded sharp ripples.
Position and locus of the mouse.
However, the activity of up to 500 neurons presented them with challenges. Yang Wannan explained that if it is two neurons, it can be represented in the x-axis and y-axis, and the data is in two-dimensional space, but 500 neurons need to be represented in a high-dimensional space.
In order to intuitively understand the data, visualize neuronal activity, and form hypotheses, Yang Wannan successfully converted the high dimension to the low dimension using the method of dimensionality reduction. Subsequently, they colored the neuronal activity in the order in which the events occurred. As Yang conjectured, the seahorse not only recorded the location, but also the sequence of events.
When neural manifolds are colored in sequence of events, the hippocampal state changes according to the order of the trial. Neural manifolds: Refers to the structure and patterns of data in high-dimensional space, which may have simpler and meaningful representations in lower-dimensional latent spaces.
Although the rat will cycle through the same place multiple times in the maze, the state of the brain will always change. Yang Wannan et al. used this characteristic of the brain to decode the representation of nearly 500 neurons to different events.
The study found that when something happened while the mice were awake, the events that caused a lot of sharp ripples were flagged and selectively replayed many times during sleep to become permanent memories. Conversely, there are only a very small number of events with or without sharp ripples that do not form permanent memories.
"We found that the sharp ripples that occur during waking are the labels that the brain decides which memories to keep and discard!" Yang said, "In the future, the sharp ripples can be adjusted according to this mechanism, thereby improving memories and even reducing people's memories of traumatic events." ”
"It's like seeing things for the first time"
Faced with the commonplace location cells in the experiment, Yang Wannan is always curious and observes them from a new perspective.
Her sheer curiosity about the world and her spirit of courageous exploration came from her family's upbringing. Yang Wannan's parents are not parents in the traditional sense, they will take the initiative to ask the teacher to let the children do less homework, and take the sisters to go hiking and camping every weekend, fully respecting and understanding their "strange" ideas.
Similarly, Yang Wannan's twin sister is also a doctor of neuroscience and is studying at Brown University in the United States.
Yang Wannan (left) is at MIT when her father and twin sister visit her in the dormitory.
Yang Wannan (right) visits her mother and twin sister in Boston during her stay at MIT. Image courtesy of the interviewee
Although she "stumbled" along the way, Yang Wannan's thinking and exploration never stopped.
She learns the wisdom of the spirit through philosophy, shapes her thinking, and draws wisdom from the sciences, and she explores her personal interests, truths, and mysteries in the sciences, and also broadens her horizons, extracts strength and inspiration from the lines of literature.
In the challenging and confusing days of scientific research, Yang Wannan likes to read biographies of scientists. She remembers what Santiago Ramón Cajal wrote in his book "Advice to Young Scientists":
“Look at things as if for the very first time.” That is, admire them afresh, disregarding what we remember from books, stilted descriptions, and conventional wisdom. We should infuse the things we observe with the intensity of our emotions and with a deep sense of affinity. We should make them our own where the heart is concerned, as well as in an intellectual sense. Only then will they surrender their secrets to us, for enthusiasm heightens and refines our perception.
"It's like seeing things for the first time." That is, to appreciate them with fresh eyes, and to discard what we remember from books, rigid descriptions, and conventional wisdom. We should infuse what we observe with strong emotions and deep love. We should make them our own, both mentally and intellectually. Only then will they reveal their secrets to us, because enthusiasm raises and perfects our perception.
Yang Wannan has always adhered to this: always curious, always full of enthusiasm.
Related Paper Information:
Hatpas://doi.org/10.1126/Science.ADK8261