Lousy sleep. A foul mood. Frequent trips to the refrigerator. They’re common signs of stress, but Sora Shin sees something more.

Shin’s new laboratory at the Fralin Biomedical Research Institute at VTC examines how stress alters brain circuits, causing lasting changes to mood, behavior, and, in some cases, overall mental health.

“People show a dynamic range of responses to acute and chronic stress. Some people have sleep disturbances, while others feel more tired than usual. Likewise, some people may overeat and others lack an appetite,” said Shin, who is an assistant professor with the Fralin Biomedical Research Institute and Virginia Tech’s Department of Human Nutrition, Foods, and Exercise in the College of Agriculture and Life Sciences.

According to the American Psychological Association, 75 percent of adults in the United States experience stress. But when it comes to treatment, there isn’t a one-size-fits-all solution. By revealing what happens when brain circuits become impaired, Shin hopes her research will one day lead to more precise treatments for psychiatric disease.

“We first look at a functional difference in behavior and trace it to a brain region where the change originated. Then we search for therapeutic targets to correct signaling errors within a defined brain circuit,” Shin said.

Shin’s team uses a combination of in vivo imaging techniques to see what’s happening at a microscopic scale in freely moving mice. The scientists image calcium to reveal neuronal activity and detect cells with impaired calcium signaling. Next, they use a variety of techniques to modulate cell activity in that select group of impaired neurons and trace the behavioral effects.

“We’re investigating specific circuit mechanisms of psychiatric disease and hope that one day we’ll use this knowledge to develop targeted medications that correlate with an individual patient’s unique experience and symptoms,” Shin said.

Not all forms of stress lead to mental illness. As part of the body’s normal reaction to change, stress can be positive, playing an essential role in evolution and adaptation. Stress helps organisms survive by keeping them alert and helping them detect danger.

But chronic stress without relief can come at a cost to mental and physical well-being.

Shin first-authored a 2015 study that sheds light on this phenomenon, studying how chronic stress leads to depression. The study, published in Nature Neuroscience, revealed how a chemical signaling flaw in the brain’s nucleus accumbens may be linked to stress-induced depression. When Shin and her colleagues injected a virus carrying genetic instructions to compensate for a missing gene, it increased levels of a key protein involved in regulating reward. The virus did the trick: as levels of the protein increased, the circuit was corrected, and depressive symptoms waned.

Shin and her team revealed how defects in a precise signaling pathway increased the risk of chronic stress-induced depression and then alleviated those symptoms once again using a drug to mimic the virus’s effects and correct the circuit.

Other forms of chronic stress during phases of brain development can also have long-lasting effects on mood, personality, and overall mental health. People who experience early life stress, characterized by abuse or neglect experienced during childhood, are at higher risk of gaining dysfunctional social behaviors as adults. 

Shin and her colleagues showed that mice who experienced early life stress and had trouble socializing as adults could gain normal social skills if a specific type of neuron was activated.

First-authored by Shin, the 2018 paper published in Neuron showed that mice with social impairments had blunted brain cell activity in response to social interaction in the lateral septum – a brain region that regulates behavioral stress response. When the researchers used a technique called optogenetics to activate specific neurons using light stimulation, the social impairments vanished. The scientists yielded the same results when they used a drug to manipulate the same pathway.

“Many scientists have studied how someone’s genes might predispose them to mental illness, and that is important, but I am interested in how gene expression is altered by our environment,” Shin said.

Prior to moving her laboratory to Virginia Tech, Shin was a postdoctoral fellow at the University of California, San Diego, where she received the Kavli Institute for Brain and Mind innovative research grant award in 2018.

Born and raised in South Korea, Shin completed her bachelor’s degree in biology at Chung-Ang University, master’s degree in physiology at Sungkyunkwan University College of Medicine, and doctoral degree in medical science at Yonsei University College of Medicine.

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