Fudan Scholar Explores the Mystery of Brain Neural Network Formation

After more than three years of dedicated research, a team led by Associate Professor Yu Yongchun from the Institute of Neurobiology at Fudan University, in collaboration with the team of Shi Songhai at the Sloan Kettering Institute in New York, USA, has made significant progress in "research on the development of brain neural circuits." This achievement is the first to discover that information exchange mediated by "electrical synapses" between brain neurons plays a crucial role in the development of neural circuits in the cerebral cortex. This research not only provides important insights for scientists to delve deeper into the mystery of how the cerebral cortex neural network is formed, but also offers new ideas and targets for the diagnosis and treatment of diseases related to abnormal development of brain neural circuits (such as childhood epilepsy, autism, intellectual developmental delay, etc.). Recently, this achievement was published online in the world's top scientific journal, Nature.

The cerebral cortex is a complex network composed of tens of billions of neurons. The part where one neuron in the brain contacts another is called a "synapse." It is the site where neurons functionally connect and the key site for information transmission. Scientists refer to the process where presynaptic cells in the brain transmit information to postsynaptic cells by releasing special chemicals as chemical synapses; they refer to information transmission via electrical signals as "electrical synapses." "Electrical synapses" are generally considered to play an important role in information exchange between neurons.

For many years, neuroscientists have been considering and studying a major question: How are the neural synaptic circuits in the cerebral cortex formed? Are there any basic rules governing the formation of these neural circuits? Research shows that during the early development of the mammalian cerebral cortex, there are numerous "electrical synapses" between excitatory neurons. However, as the cerebral cortex continues to develop, the "electrical synapse" connections between neurons gradually disappear, replaced by chemical synapses.

To explore the mystery of the brain's "electrical synapses," researchers including Yu Yongchun first elucidated the important role of "electrical synapses" in the development of cortical neural circuits by altering the "electrical synapse transmission" between excitatory neurons. In the study, they discovered an interesting phenomenon: In recordings of neural circuits during early development, sister neurons with high relatedness had tighter "electrical synapse" connections than non-sister neurons. As development progressed, the "electrical synapse" connections between sister neurons gradually decreased, and "chemical synapses" gradually replaced "electrical synapses." So, what is the role of the "electrical synapses" expressed early by sister neurons?

Yu Yongchun and others further found that "electrical synapse connections" play a key role in the synchronized firing of sister neurons. To further study the impact of "electrical synapses" on the development of chemical synapses, Yu Yongchun and others cleverly used molecular biology methods to selectively close the "electrical synapse" channels of sister neurons. A surprising scene occurred: after the channels were closed, the chemical synapse connections between sister neurons decreased significantly, while the chemical synapse connections between non-sister neurons were unaffected.

The above research results indicate that the development of neural circuits in the cerebral cortex follows certain rules: the higher the neuronal relatedness, the easier it is to form synaptic connections. More importantly, neuronal relatedness is linked by "electrical synapses." This achievement first reveals the causal relationship between "electrical synapses" and "chemical synapses." It has cracked the "secret language" of mutual communication between neurons during the development of cerebral cortical circuits, taking an important step forward for humans to deeply explore the mysteries of the brain, and has significant meaning for the diagnosis and treatment of related diseases caused by abnormal development of neural circuits.