The brain is full of mysteries and wonders. It is the most delicate and complex organ in the human body. Fragile yet powerful, the brain coordinates the functions of almost all other organs in the human body. It receives information from all over the body, makes decisions and sends commands to accomplish necessary tasks. Different regions of the brain are responsible for different functions such as movements, language, vision, learning, memory and so on. These regions are well linked to form complicated circuits to process information. A neuron, by an average number of about 100 billion, is the basic functional unit of the brain. They have very fine structures called synapses to send information to or receive information from other neurons. Each neuron can possess as many as 10,000 synapses, which means a neuron can make as many as 10,000 connections with others. Irregularities in synapse formation or synapse activity could possibly destroy the very basis of brain functions, leading to brain disorders or psychiatric diseases.

Seeking for the linkage between synapses and psychiatric diseases, Our group in the Hong Kong University of Science and Technology has been investigating synapse formation and synapse function for many years. In this project, we focused on the hippocampal region of the brain which is associated with direct learning and memory abilities, and studied the synapses of the hippocampal neurons using mice and rats as the animal models. By using molecular markers, we were able to trace the development of the neurons and stamp the critical time windows for synapse formation and synapse functioning under a microscope. We found that the proteins, thrombospondin and neuroligin1, could together accelerate the process of synapse formation, but only during the early development stage. Accordingly, neuroligins are a critical protein family in the synapse structure, and help to ligate the synapses from two neurons together. They have been found to be associated with autism. It is interesting to discover that this accelerating function only works during early synapse formation, because autism first appears during infancy or childhood. It implies that early synapse formation can be a target of autism research.

　

　

Furthermore, we found the mechanism through which synapses maturate from a newly formed naive synapse into an active synapse. By culturing hippocampal neurons and other cells together, we were able to construct a system of artificially-induced synapses and study the maturation of those new synapses. Taking advantage of this coculture system and other genetic manipulating techniques, we found that the protein PICK1 could recruit a critical synapse protein AMPA receptor onto the naive synapses, thereby accomplishing the synapse maturation.

Even though our current work is focused on the hippocampus, it is highly possible that the mechanisms of synapse formation and synapse maturation elucidated in this project are general across most regions of the brain because the critical proteins we investigated are all highly expressed in the brain and distributed in most parts of the brain. Some of these synaptic proteins have long been shown to be involved in psychiatric diseases and mental retardation. Hopefully we can eventually find the bridge between synapse construction and brain functions. Only then will we be able to understand how a screw sunk Titanic.