Don't want to socialize when you have a cold? Immunity affects the nervous system

When Gloria Choi planned to set up her own research lab at MIT about 10 years ago, she thought it would be great to find a sub-program to work with her husband, an immunologist at Harvard Medical School
.

The two scientists decided to investigate a surprising observation they heard in graduate school: A large Danish study showed that severe infections in pregnant women were associated
with a much higher risk of autism in their children.
Their study of this phenomenon, known as maternal immune activation, has since become a cornerstone of both of their research projects and has yielded key insights
into the mechanisms behind this increased risk.

Choi, Mark Heyman, associate professor of career development in brain and cognitive sciences and recently offered tenure at MIT, and her husband, Jun Xu, an associate professor of immunology at Harvard University, have also demonstrated that an immune molecule called IL-17a can temporarily reduce some behavioral symptoms
of autism.
This immune molecule is produced
by immune cells during fever.

Choi hopes that this research will one day lead to new ways to treat autism as well as depression or anxiety
with immunotherapy.

"Understanding the flow of information between the immune system and the nervous system can help us understand the causes of neurological diseases and will help us design treatments
that no one has thought of before.
" This will be a completely new toolkit that we can think about treating neurological disorders," Choi said
.

Born in South Korea, Choi moved to Southern California with his family as a teenager and enjoyed math and science
in high school.
As a non-native English speaker, she felt more comfortable in these subjects than in the humanities
.

"I like working with numbers because it's logical
.
2 plus 2 equals 4
.
There is no ambiguity," she said
.

At the University of California, Berkeley, she majored in biology and business
.
After completing her undergraduate degree, she went to Caltech, where she earned her PhD in biological sciences, working with David Anderson
.
Anderson, a stem cell biologist, shifted his lab's focus to neuroscience, while Choi embarked on one of the lab's earliest neuroscience projects, studying the circuits
that control animals' inherent social behavior.
As a postdoc at Columbia University, she continued her work with Nobel Prize winner Richard Axel in neuroscience, studying the neural circuits that link smell to specific memories
.

While Choi was at Columbia, she and Xu also began preliminary research
on maternal immune activation.
They expanded the study
after they established their own labs at MIT and Harvard.
The study found that exposure of mice to IL-17 during fetal development caused abnormalities in a region of the brain called S1DZ, which is part of the
somatosensory cortex.

These abnormalities can lead to autism-like symptoms, such as repetitive behavior and impaired social skills, which can be reversed
by restoring normal activity in S1DZ.
Choi is now trying to further explore how S1DZ affects social behavior
.
S1DZ is related to proprioception, which is how people perceive
the position of their body in space.

"Proprioception is really all about yourself, but why is that feeling so important when you interact with others?" She said
.
"I think it's one of the hardest questions in our lab, but it's one we really have to answer because we discovered it and we felt a responsibility to understand why
.
"

Diseases and behaviors

Choi also expanded her research to explore other aspects of
the interaction between the immune system and the nervous system.
As part of her "Sick Behavior" study, she asked questions such as why we sometimes feel anxious or depressed when we are sick, and how does being sick affect our interactions with others.

"When we have the flu or a cold, we experience all these symptoms: we have headaches, we can't think well, we are tired
.
We didn't want to go out or hang
out with friends.
For a long time, it was thought that this was just a side effect of fatigue, but now more and more people are discovering that it is actually an active process of
dialogue between the immune system and the brain.
It makes sense – when you're sick, you don't want to go out and socialize, which definitely protects the community
.
”

She found evidence that some cytokines produced by the immune system can enter the brain, activating receptors
involved in controlling social behavior.
She also found that in mice, when males met a diseased female, they did not try to mate with her, which exceeded their usual mating instincts
.
This behavior appears to be controlled by a circuit in the amygdala that detects the diseased animal's distinctive smell and triggers warning signals to keep people away
.

Choi, who is not a natural adventurous person, says her life at MIT motivated her to explore more adventurous, unconventional research questions
.

"I've decided to do a lot of risky things, and that's not always a wise thing to do," Choi said
.
"I think it's an environment that awakens my fearlessness and helps me to study issues that aren't safe, but fundamentally important and biologically really interesting
.
"