A UCLA study has mapped a critical brain hub in mice that regulates stress responses and social behavior, shedding new light on the neural roots of psychiatric conditions such as post-traumatic stress disorder, depression and anxiety.
The study , published in the journal Nature, reveals how a region of the medial prefrontal cortex, which has long been linked to personality and emotional regulation, integrates information across the brain to coordinate physiological and behavioral responses.
The findings help explain classic cases of personality changes and open new paths toward understanding and treating complex neuropsychiatric disorders, said lead author Dr. Hong Wei Dong , professor of neurobiology at UCLA Health and director of the UCLA Brain Research & Artificial Intelligence Nexus.
"This work gives us a wiring diagram of one of the brain's most mysterious control centers," said Dong. "It provides a foundation for developing targeted therapies for stress-related and social dysfunction disorders."
For more than 170 years, the case of a railroad worker named Phineas Gage whose frontal lobe injury dramatically altered his personality has symbolized the mystery of how the brain regulates emotion and behavior. Gage became impulsive, socially uninhibited and struggled with decision-making. These symptoms helped scientists identify the prefrontal cortex as a key regulator of personality, social behavior and emotional control. However, the detailed neural circuits and mechanisms underlying these changes have remained elusive.
In his study, Dong's team used advanced genetic labeling, 3D brain imaging and AI-driven circuit mapping to chart the intricate wiring of the medial prefrontal cortex (MPF or mPFC) in mice, including the dorsal peduncular area (DP) and infralimbic area (ILA). These regions act as hubs that integrate sensory and internal body signals to coordinate emotional and physiological responses. The findings reveal how these hubs govern emotional stability and stress regulation, offering a cellular-level blueprint of circuits that are conserved in the human vmPFC.
"Our work closes a critical gap in understanding how these brain regions orchestrate complex behaviors and stress responses," said Dong. "By identifying the precise circuits involved, we open the door to developing better diagnostic tools and targeted therapies for psychiatric and neurological disorders."
The findings have broad implications for public health, offering new hope for millions affected by neuropsychiatric conditions worldwide. By translating this foundational knowledge into actionable insights, Dong said the findings can help drive the next generation of treatments for emotional and stress-related disorders.
