CSHL’s Li looks for clues to understand traumatic stress

CSHL’s Li looks for clues to understand traumatic stress

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Bo Li looks closely at red and green colors. He is not preparing Christmas decorations, but rather is looking at the way different neurons in a region of the brain light up in response to an increase or decrease in fear.

An associate professor in the Neuroscience Department at Cold Spring Harbor Laboratory, Li is studying a small area in the mouse brain called the amygdala. His results may help guide pharmaceutical companies and other researchers as they look for ways to help people suffering with post-traumatic stress disorder.

In the central amygdala, he found two cell populations that likely play some role with fear. One of those cell populations promotes fear. He believes the other suppresses fear. Ongoing studies, he said, will provide answers about the other cells soon. Once he understands both, he will look for ways to affect their activity.

Understanding fear responses is just one of the areas where Li studies neurons in the brain. He also does research on animal models of depression and schizophrenia, hoping to find differences researchers can exploit to provide early detection, treatment and prevention.

Fritz Henn, a visiting professor at Cold Spring Harbor Laboratory who collaborated with Li when Li was a post-doctoral fellow, said he is a “rising star in neuroscience research.”

In post-traumatic stress disorder, people who witness or experience stressful and potentially life-threatening experiences develop a sustained level of fear, even after removed from stresses like the life-and-death struggles of war. This trauma can diminish the quality of life as people struggle with emotional scars that don’t seem to heal.

By looking at the neurons of mice, Li is able to use genetic technology to explore an area that contains about 10,000 neurons. He uses scientific advances that enable him to separate neurons in different categories. These different types of neurons are labeled by a marker, which glows in green, yellow or red. He can also use viruses that specifically recognize these neurons and enable him to see a higher or reduced activity level for these neurons in a fear response.

Using an optical fiber that is about 150 microns, which is about the thickness of a human hair, Li can shine a light on the amygdala to see signals that are then collected through a computer. His analysis allows him to record changes in the signals sent by these different types of cells. Henn called Li’s research “state of the art.”

By collaborating with other scientists at Cold Spring Harbor Laboratory to do gene sequencing, Li can look at what other proteins are expressed by these different cells.

“It’s just a matter of time to gather the data and come to conclusions,” he said. He believes this research will make substantial scientific progress in the next five years. The clinical applications will likely take longer, he predicted.

The amygdala is an area that scientists have known for a long time controls emotion and emotional memory. As a result, researchers on Long Island and elsewhere in the world are putting considerable energy and time into understanding the specific cellular functions in this region.

His work on schizophrenia presents other challenges because it’s difficult to mimic the kind of symptoms humans exhibit, including hallucinations and reasoning problems.
Li is looking at the genes linked to schizophrenia and finding similar genes in mice.

“Going from genes to behavior is a big gap,” he said. “We need to fill that in.” He is working on genes in his lab that he knows cause problems in some brain circuits to understand depression as well.

“We know a particular circuit in the brain [called the lateral habenula circuit] is important for reward, learning and punishment,” he said. “When this circuit is impaired, it can cause depression.”

Li lives on campus at Cold Spring Harbor with his wife, Shirley Guo, who is also a scientist and works for Kadmon, a biotechnology company in New York City that is developing medicines for a range of diseases and provides treatment of hepatitis C. The couple have an 11-year-old daughter, Serena, who is an avid tennis player.

Li called Cold Spring Harbor a “fantastic environment” and said it is “one of the best in the world for doing science.”