MIT Scientist Yingxi Lin on Brain and Memory Research

By David Li,

There was another Lin working hard at Harvard’s Boston Children’s Hospital when Jeremy Lin was playing basketball for Harvard.

In December 2011, journal Science published a long research paper titled Npas4 Regulates a Transcriptional Program in CA3 Required for Contextual Memory Formation, which revealed the key controlling factor of the Npas4 gene for short-term memory converting into long-term memory in the brain. This paper helps further understanding of mechanism of how short-term memory turning into long-term memory in the brain, and will have far-reaching impact on the research and treatment of Alzheimer’s disease, amnesia and other neurological disorders.

Yingxi Lin (right) in the laboratory with Yonatan Cooper (left) and Ross McKinney.

Early January 2012, I visited the Lin Lab at MIT McGovern Institute for Brain Research, and had an interview with Npas4 gene discoverer Dr. Yingxi Lin. Just returning to work after maternity leave, Lin brought her 8-week-old daughter to office. While talking with reporter about her research and her educational background in physics, Lin walked to the side of the cradle where her daughter was sleeping from time to time to check on her.

Physics Studies

Dr. Lin told me that she was born to a family of intellectuals of Guangxi University in Nanning, Guangxi province, China. Maybe it was the genes from her math professor mother, Lin showed mathematical talent at early age. Lin graduated Nanning No. 3 Middle School in 1986,  and enrolled into Tsinghua University. From then on, Lin has studied and researched at the world’s top universities. She received bachelor and master degrees in Engineering Physics in 1991 and 1994. During the master’s studies, Lin involved in signal acquisition and exploration of biological equipment over from the system.

In 1994, Lin received a full scholarship from Harvard University to pursue a PhD degree in Physics. “I wanted to learn medical imaging. In 1995, I enrolled in an MIT class of magnetic resonance imaging (MRI), and learned to use the NMR spectrometer to observe the molecular structure. I also became interested in biological organisms, like protein. After graduating with doctor’s degree in physics from Harvard at end of 1999, I decided to pursue a post-doc position in neurobiology,” Lin said with a smile.

Switch to Biology Runway

In 2001, after waiting for a year for bench, Lin got her wish and entered very popular Prof. Greenberg’s lab at Harvard-affiliated Boston Children’s Hospital. As head of Harvard Medical School Neurobiology Department, Greenberg’s selection standard was very high. Lin recalled: “I was surprised that Prof. Greenberg took me to his lab. He told me years later that he valued my training in physics, and thought I would be able to pay attention to details and perform experiments precisely. Indeed, like Prof Greenberg, I am a very detail oriented person.”

Lin’s performance proved that Prof. Greenberg’s instinct was correct. While she worked at Children’s Hospital, Lin discovered Npas4 gene which is a common gene in mammals, and found that Npas4 gene was particularly active in the hippo campus of the brain.

Launch Her Own Lab

In January 2009, Lin joined MIT McGovern Institute to establish her own lab with start-up funding provided by the MIT. Later on, she also received research grants from National Institute of Health. The basis of this Science paper was lab results by Lin and five students, post-docs and technicians in the past two years. They worked seven days a week, 10 hours a day for this research project according to Lin.

Lin mentioned the name of this experiment is contextual fear conditioning. If researchers put a mouse in a new cage, within only 3 to 4 minutes, it will soon remember this new cage. And if at the same time, the mouse was electrically shocked through the metal cage for 3-4 times, each time lasting 2 seconds, then the mouse would remember this cage was dangerous. The next time researchers put it in the same cage, it would corner itself in the cage as if there was a cat in the cage.  Under normal circumstances, this fear of the cage lasts for months or even the mouse’s lifetime. Then the researchers tried a mouse whose Npas4 gene had been removed, and repeated the same experiment. This time, the mouse’s fear of the new cage only lasted for five minutes. Finally, the researchers implanted Npas4 gene back to the mouse’s brain, the mouse then behaved like normal again, and could remember the terrible cage for long durations.

After describing the above experimental phenomena, Lin’s paper did further analyses of the underlying biological neural theory, and explored how the Npas4 gene controlled short-term memory converting into long-term memory in the brain.