How Conditioning Can Help Overcome Social Disability… Message of Hope from a Neuroscientist

Humans are social animals. Our actions influence others, and the actions of others impact us. We live constantly interacting with different people in society. So, where does human sociality come from? Some say it's an innate instinct from birth, while others argue it's a skill learned through education from an early age.

Dr. LEE Doyun, a research fellow at the IBS Center for Cognition and Sociality, states, "The secret of sociality lies hidden in our brains." Indeed, brain function is closely associated with sociality. called Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has been known to impair social behavior and interaction with other individuals.

The brain, with its complex network of various types of nerve cells, remains unknown even to scientists. Due to its intricate structure and functions, in-depth brain research only began recently with the development of advanced experimental techniques. Consequently, many mysteries persist regarding the connection between brain disorders and sociality.

Recent research by Dr. Lee has provided a clue that many scientists have been seeking. He identified cells in the brain responsible for recognizing others and discovered their close association with sociality. Furthermore, he revealed that the social impairment caused by ASD can be restored through repeated education. This suggests that while sociality may be innately influenced by the brain, the impairment can also be overcome through effort.

He expressed, "This research presents the scientific basis for current ASD treatments and suggests potential new therapeutic approaches for ASD. I hope this study can bring hope to those suffering from ASD."

We had the opportunity to meet with Dr. LEE Doyun to discuss the significance of these research findings.

Q: Could you please introduce yourself?

A: I received my bachelor's and master's degrees in Molecular Biology from Seoul National University and later pursued a Ph.D. in the Department of Physiology at Seoul National University's College of Medicine. Following that, I worked as a postdoctoral researcher at the Janelia Research Campus of the Howard Hughes Medical Institute (HHMI) in the United States, where my research focused on the hippocampus, a vital area of the brain associated with long-term memory and spatial recognition. Since 2015, I've been working at the Center for Cognition and Sociality within the Institute for Basic Science (IBS), focusing on how cells recognize individual information and their role in social behavior.

Q: What is the Center for Cognition and Sociality at IBS?

A: The IBS Center for Cognition and Sociality is dedicated to researching cognition, sociality, and brain disorders based on neuroscience. It was one of the first research groups established when IBS was founded. Led by Directors C Justin LEE, who studies astrocytes, and KANG Bong-Kiun, who focuses on learning and memory, the Center consists of four research groups. Cognitive functions play a crucial role in various brain disorders and social behaviors, and our Center aims to understand how brain functions and discover treatments for brain disorders.

Q: What is your main area of research?

A: I have spent a considerable amount of time researching the hippocampus. The hippocampus plays an important role in memory, particularly episodic memory. Episodic memory involves the ability to recall events in a way that can be verbally expressed, such as remembering whom you met and what you did a week ago. On the other hand, memories related to non-cognitive functions, such as riding a bicycle, are called procedural memory.

There are important elements of episodic memory, commonly referred to as the six principles. Among them, location plays a very important role. Within the hippocampus are special cells called “place cells” that are responsible for recognizing location information. Rat brains have particularly large hippocampus, which gives these animals an excellent ability to process spatial information. In fact, in 2017, scientists who discovered “place cells” received the Nobel Prize in Physiology or Medicine.

Q: How does hippocampal research relate to social behavior?

A: I believed that the hippocampus could process all elements of episodic memory, not just places. I hypothesized that the hippocampus recognizes various types of information, combines them, and forms memories. Episodic memory is crucial for social behavior, and, therefore, it makes sense for the hippocampus to have the ability to recognize other individuals. Indeed, in May of this year, we found nerve cells in the mice hippocampus that were activated only when encountering specific individuals.

Q: You recently announced research findings related to Autism Spectrum Disorder (ASD). Could you share more about that?

A: I aimed to provide scientific evidence for behavioral therapy for ASD. ASD is a brain disorder that presents challenges in social behavior. Studies of the prefrontal cortex, which is another crucial part of the brain, show that individuals with ASD do not exhibit significant differences in their reactions to social and non-social signals. The challenge is that there is currently no definitive cure for ASD. Although some symptoms can be alleviated, there is no cure for the fundamental disorder.

Therefore, individuals with ASD undergo behavioral therapy from a young age. However, there is still debate among experts about the effectiveness of behavioral therapy. Some view it as effective only in the given context, while others believe it enables social behavior in new situations as well. Scientific evidence supporting how effective behavioral therapy is in treating ASD has been lacking.

Q: What prompted you to start this research?

A: The principle of behavioral therapy involves rewarding social behavior and enabling it in real-life situations. The question was whether the brain area governing social behavior could be restored through behavioral therapy and whether the restored brain function could be used in different situations. I felt that an experiment was needed to investigate if the brain areas responsible for social behavior could be restored through behavioral therapy and whether the restored brain function could be used in other situations.

Q: Could this research lead to a breakthrough in overcoming ASD?

A: Mice recognize other mice through smell. We exposed mice with ASD to signals from both other mice (social signals) and non-mouse-related odors (non-social signals) and studied the signals emitted from the prefrontal cortex. While normal mice reacted differently to these signals, ASD mice were unable to distinguish between the two signals. Their brain was not capable of processing social signals.

When we repeatedly trained the ASD mice to associate the smell of the reward with meeting another mouse, their prefrontal cortex's ability to distinguish social and non-social signals improved. This positive result indicates that behavioral therapy can be helpful in overcoming ASD.

Q: How is this research being received in the academic community?

A: It has been acknowledged as a significant research result. There are, however, aspects of this study that I find personally lacking. We did not conclusively show which neural circuits behavioral therapy uses to restore social behavior. Other experts who reviewed the paper also pointed out this limitation.

Nevertheless, the editorial team chose to publish this paper because it provided neurological evidence that behavioral therapy can aid in overcoming ASD. It has been considered an important paper as it could pave the way for follow-up studies on methods to overcome autism based on this research.

Q: Were there any challenges during the experiments?

A: Communicating directly with mice posed the most significant challenge. To study behavior, the tasks need to be complex, because it is crucial to controlling the variables. However, when the task is more complex, it is more difficult for mice to perform them. Initially, even getting mice to drink water as a reward was challenging. If it were humans, we could explain with words, but mice have to be taught through experiences. It was difficult alone to obtain mice with autism, and trying to find mice that could perform the tasks made the experiment even more challenging. This was the most significant difficulty in this research.

Q: Do you personally create the equipment used in experiments?

A: Making custom equipment is essential as the task list needs to be tailored to the necessary experiments. Initially, it wasn't easy because it was not something I was used to doing. I started by teaching myself through YouTube, and now I'm proficient enough to create simple software. As the experiments became more complex, I found myself often needing the help of surrounding experts.

Fortunately, there are many experts in the Daedeok Research and Development Special Zone, so finding assistance is relatively easy. Recently, I even received help from the parents of my children's friends. Many people I meet spontaneously from children’s events happen to be researchers also, so building connections in this way has been quite helpful.

Q: Given your focus on studying social behavior, you must have a keen interest in the behavior of those around you in daily life.

A: While not directly related to research, there are fascinating phenomena that can be observed in daily life. One such phenomenon in social animals, including humans, is called "social orientation." For example, on highways, it's common to see trucks with stickers resembling eyes on the back. This is quite noticeable, and even newborns focus on eye-like shapes. It's an instinctive behavior of our brains.

There's also the "chameleon effect," a behavior where individuals mimic the behavior patterns of the group they belong to. My family is originally from Gyeongsang Province, but we currently live in Daejeon. As a result, I find myself using the Chungcheong Province dialect more often. It's an unconscious behavior to enhance familiarity.

Q: What are your future research plans?

A: Given that the primary research topic of our group is social signals, we plan to continue research on ASD. I am particularly interested in research related to reward. The relationship between reward circuits and the processing of social information is a major focus of current neuroscientists. We plan to follow up on this research by exploring how behavioral therapy restores brain function, which we were unable to explain in this study.

Q: Any final thoughts you would like to share?

A: I hope that my research not only unlocks the secrets of brain function but also contributes to the conquest of diseases. Many brain disorders still have unknown causes. Without understanding the causes, we cannot find treatments. I will continue my research for the sake of improving people's lives.

LEE DOYUN LAB AT IBS

https://www.ibs.re.kr/glia/

<Reference>

Reward learning improves social signal processing in autism model mice

Cell Reports | VOLUME 42, ISSUE 10, 113228, OCTOBER 31, 2023

https://www.cell.com/cell-reports/fulltext/S2211-1247(23)01240-8