The Role Of SIRP Alpha-CD47 Signal In The Synaptic Development Of The Central Nervous System(CNS)

Proper synaptic connections are essential for the normal function of the brain.The synaptic formation of the central nervous system(CNS)is a rather complex process,and the mechanisms and molecules involved are diverse.The complexity is the formation of numerous synaptic connections that connect nerve cells in highly specific ways.The synaptic formation of vertebrates begins in the embryonic period and continues into adulthood,which contributes greatly to learning and memory.In CNS development process,many synapses were set up,but in the end some useful synapses retained.In this process,eliminating redundant synapses is the key step in the maturation process of the synapse circuit.There is little knowledge of the highly specific alienation in central synaptic development.Microglia is akind of glial cell locating in the brain and spinal cord,which accounts for 10-15%of all cells in the brain.They are resident macrophages in CNS and are the guardians of CNS.It not only functions when it is in the CNS in disease states,but can also repair the structure of the CNS.They can take fine adjustment for the neuronal circuits and the neuron network connection,and also play a role in the formation of neural plasticity.Research shows that,under the background of the complement system in CNS,microglia plays the role of synaptic pruning during CNS development,and plays an important role in the maturity of synapses,which will affect synaptic function and synaptic plasticity.Thus,microglia can affect the ability of learning.The studies on the interaction betwen signal regulatory proteins(SIRP alpha)and CD47 are relatively clear in the immune system,but their role in the development of CNS synapses is not very clear.Almost all cells express CD47,and SIRPa is mainly expressed by myeloid cells and stem cells,or neurons.In neurons,SIRPa expression level is different,but it has high expression in abundant synapse regions,and is also expressed in microglial cells.The interaction between SIRPa and CD47 conveys the inhibitory signal of ’Don’t eat-me".However,at present,the influence of the interaction between SIRPα and neuronal CD47 in microglia and synaptic development in CNS is still not clear.This paper,by using electrophysiological and immunohistochemical methods and so on,respectively studied the synaptic growth and contact strength of WT,SIRPα-/-,SIRPα.ct-/-and CD47-/-mice.We first study the main role of SIRPa and microglia in the development of synapses in CNS.We found that the absence of SIRPa could promote the phagocytosis of microglia,and the strength of synaptic connections and synaptic plasticity were wakened,and the learning and memory ability of mice was decreased This is of great importance to elucidate the development mechanism of CNS.