According to the University of Science and Technology of China, Professor Bi Guoqiang's team published a groundbreaking research result in the field of neuroscience in the journal Science on the 17th, revealing the "microscopic code" for efficient information transmission in the brain and providing a new perspective for the mechanism research of related brain diseases. It is reported that Professor Bi Guoqiang's team has gone through 15 years of continuous research and development. Based on the self-developed millisecond level time-resolved cryo electron microscopy technology, they have successfully captured the complete dynamic process of synaptic vesicle release and rapid recovery, and proposed a new "kiss contraction escape/fusion" model, solving a key controversy in the field of neuroscience that has lasted for half a century. The realization of brain function relies on efficient and precise synaptic transmission between hundreds of billions of neurons. As a carrier of neurotransmitters, the release mechanism of synaptic vesicles has always been an important issue in the field of neuroscience. Since the 1970s, the scientific community has formed two opposing models around the mechanism of vesicle release: "full fusion" and "kiss escape". However, due to the fact that vesicle release occurs at the millisecond time scale and structural changes occur at the nanoscale, traditional techniques are difficult to capture its instantaneous dynamics, which has plagued the field of neuroscience for 50 years. To overcome this challenge, Professor Bi Guoqiang's team collaborated with multiple domestic and international teams to develop an in-situ cryo electron microscopy technology with millisecond time resolution. They innovatively combined optogenetic stimulation with input based rapid freezing methods to achieve millisecond level "dynamic freezing" of neuronal synaptic transmission processes. The team introduced that in specific experiments, they expressed photosensitive proteins in neurons and triggered synaptic vesicle release by precisely stimulating action potentials with lasers. Subsequently, the electron microscope mesh carrying the sample quickly fell into the cryogen within the set time, instantly fixing the cells. By precisely controlling the time interval between lighting and freezing, the team was able to capture structural snapshots of vesicles at different stages of release (from 4 milliseconds to 300 milliseconds). The team further explained that based on the systematic analysis of thousands of sets of high-resolution 3D structural data, they found that the release and rapid recovery of vesicles are a dynamic process that can be divided into three stages - vesicles first form nanoscale fusion pores with the presynaptic membrane, also known as "kissing"; Subsequently, it rapidly shrinks into small vesicles with a halved surface area, known as "contraction"; In the end, most of the vesicles were recovered through "escape", while a few underwent "complete fusion". Intermediate contraction is a key factor that provides a structural foundation for efficient and high fidelity signal transmission in neural synapses, "said Bi Guoqiang. This achievement provides a new perspective for a deeper understanding of neural information processing, related brain functions, and disease mechanisms. Meanwhile, the development of time-resolved cryo electron microscopy technology provides an innovative platform for studying other rapid life processes within cells, such as virus invasion and cell secretion. (New Society)