□ A DGIST (President Lee Kun-woo) research team led by Professors Eom Ji-won and Ko Jae-won of the Department of Brain Science, in collaboration with Dr. Kim Jin-yeong’s team at the Korea Basic Science Institute (KBSI), identified that the mutation of the collybistin protein found in autistic patients weakens the brain’s inhibitory synaptic function and leads to communication deficiencies. The results of this research are expected to clarify the cause of autism at the molecular level and offer important clues for developing treatments for autism spectrum disorders and various other mental illnesses in the future.
□ Our brains work properly when excitatory signals (accelerator) and inhibitory signals (brakes) are balanced. If this balance is disrupted, information transfer between neurons becomes distorted, leading to neurodevelopmental disorders such as autism and schizophrenia. These signals are transmitted at junctions called ‘synapses,’ where neurons connect and exchange information. Abnormalities in the inhibitory function of these synapses have been observed in autism patients, but it was unclear which protein is responsible for this deficiency.
□ The research team received information from a joint French research team on mutations in the collybistin gene (ARHGEF9) found in autism patients and used this information to trace the molecular causes of autism. Additionally, the team developed conditional knockout mice by removing the collybistin gene from the prefrontal cortex and observed changes in synaptic structure and functions. As a result, they found specific defects only in inhibitory synapses. Excitatory synapses remained largely unchanged, but the density and signal transmission in inhibitory synapses were significantly reduced.
□ In particular, collybistin-deficient mice were normal in other behavioral indicators, but their ability to produce ultrasonic vocalizations (USV), which are used to communicate with other mice, declined significantly. This aligns with the difficulties autistic patients experience in both verbal and nonverbal communication. Based on this finding, the research team demonstrated that dysfunctional inhibitory circuits in the brain may be a direct cause of social communication deficits.
□ The research team used proteomics techniques to examine protein changes in the prefrontal cortex. The results confirmed that collybistin regulates the activity of gephyrin, a protein that stabilizes inhibitory signals in the brain. Problems in collybistin reduce the gephyrin function, which in turn impairs the transmission of inhibitory signals and causes an imbalance in brain neural signaling. This suggests that such functional disorder could be a primary cause of deficits in social communication skills, like language, observed in autistic patients.
□ Professor Ko Jae-won stated, "This study has significantly advanced our understanding of the pathophysiology of neurodevelopmental disorders, particularly autism spectrum disorder." Professor Eom Ji-won explained the significance of the research, saying, "We will expand our collybistin-gephyrin gene research to human cell models and into preclinical studies."
□ Meanwhile, Jeong Hye-ji, a postdoctoral researcher at the DGIST Department of Brain Science's Center for Synapse Diversity and Specificity (Director: Ko Jae-won), participated in this research as the lead author. The paper was published online in the international journal "Molecular Psychiatry" on October 31, 2025. This research was funded by the Ministry of Science and ICT and the National Research Foundation of Korea through the Global Leader Research Program, Basic Research Laboratory Support Program, Mid-Career Researcher Support Program, and Sejong Science Fellowship.
