z-bio 2025-01-15 993

　　With the support of National Natural Science Foundation projects (approval numbers: 81930030, 82230036) and other grants, Professor Ma Huan's team at Zhejiang University has made progress in the study of the neural plasticity mechanism of brain dynamic "charging and energy supply". The research results, titled "Boosting neural activity driven mitochondrial DNA transcription coupling improves cognition in aged mice", were published in the journal Science on December 20, 2024. The link to the paper is: https://www.science.org/doi/10.1126/science.adp6547 .

　　As the core organ of dominant thinking and consciousness, the high efficiency and low consumption of the brain is the goal that artificial intelligence technology strives to imitate, and it is also the peak that human technology has not yet reached. Meanwhile, the regulation of brain energy is closely related to human health, and its imbalance is considered a key risk factor for neurological diseases. Whether it is the energy shortage caused by high energy consumption in the development of artificial intelligence or the severe challenges brought by an aging society, they are major challenges that humanity must face for survival and development today. From a scientific perspective, understanding how the brains of mammals integrate the fundamental elements of the life universe - energy matter information - not only provides direction for mimicking or even surpassing the brain's ability to achieve low consumption and high efficiency over the long course of evolution, but also provides an important opportunity to explore solutions to aging related problems.

　　The research team utilized molecular biology, electrophysiology, and behavioral techniques to discover that there is an age-related coupling between neural activity and mitochondrial DNA (mtDNA) transcription, which differs from the classical neural activity gene transcription coupling in the nucleus (E-TCnuc). E-TMico utilizes molecules traditionally associated with E-TCnuc to regulate mtDNA expression in regions closely related to synaptic activation. In both in vitro and in vivo models, blocking E-TMito impairs activity driven mtDNA expression and severely damages neuronal energy reserves, reducing the ability to meet synaptic transmission needs. Further research has found that elderly mice exhibit activity dependent reductions in mitochondrial calcium signaling and mtDNA expression, suggesting age-related decline in E-TMito. In elderly mice, the sustained activation of mitochondrial cyclic adenosine monophosphate effector binding protein can restore activity dependent mtDNA expression, increase neuronal energy reserve, and enhance memory function (Figure).

　　This study discovered a novel coupling mechanism in which the neural activity of the brain during information processing can drive mitochondrial gene transcription, and elucidated the neural plasticity mechanism of the brain's dynamic "charging and energy supply". This achievement provides a new direction for understanding the "energy-saving" and anti-aging effects of information processing.