Rewrite the textbook! Science: Scientists may find new synaptic structures.

Click the blue word to focus on our microglia, as immune cells in the brain, to dynamically monitor the brain microenvironment through its active branches, just as physicians do in physical examination.however, most studies have focused on the interaction between microglia and synaptic structures, including the ultrastructure of axon terminals and dendritic spines, which are generally considered to be the main form of interaction between microglia and neurons.different from synapses, the cell bodies, axons and dendrites of neurons are relatively stable. However, microglia are involved in the migration and differentiation of neural precursor cells, cell survival and programmed cell death, adult neurogenesis and phagocytosis of damaged neuronal bodies.therefore, the interaction between microglia and synapses may not fully explain how microglia dynamically monitor and influence neuronal activity.December 12, 2019, the research team of neuroimmunology laboratory, Institute of experimental medicine, Hungarian Academy of Sciences published an article in the journal Science, and found that there is a new functional connection between microglia and neuronal bodies.(this paper was first published on biorxiv without peer review on April 13, 2019). In order to fully observe the interaction between microglia and neurons, the researchers electrically transferred pcag IRES tdtomato plasmid into CX3CR1 GFP mice to observe the contact between microglia and the cell bodies of cortical neurons 2-3 under a Biphoton in vivo microscope.surprisingly, the branches of microglia prefer to touch the previously detected sites.analysis of the trajectory of microglia showed that the average time of microglia to "physical examination" of neuronal bodies was 25 minutes, and the time of "physical examination" of dendrites was only 7.5 minutes.further quantitative analysis by confocal microscopy in vitro showed that there was "limb contact" in the bodies of microglia and 91% cortical pyramidal neurons, 96% of VGLUT3 positive neurons and 87% of albumin positive intermediate neurons; only 9% of the glutamatergic synapses and 14% of the GABAergic synapses contacted the branches of microglia.it is worth noting that 87% of the neurons in the human neocortex are also in contact with microglia.this indicates that the connections between microglia and neuronal bodies are extensive.with the deepening of the research, researchers found that microglia can sense the changes of neurons through the signal related to exocytosis.under physiological conditions, GTP and ATP are needed in the process of exocytosis, which are released from the neuronal body, and ATP (ADP) is the main driver of microglial branching movement induced by microglial purine receptor p2y12r.the combination of confocal microscopy and random optical reconstruction microscopy (storm, resolution up to 20 nm) showed that p2y12r was densely concentrated at the junction of microglia and neuronal bodies.the structure of the new junctions was further observed by electron microscopy. It was found that the microglia neuron soma junction had a unique ultrastructure, which was located in the neurons and consisted of tightly bound mitochondria, reticular membrane structure and cystic membrane structure.this connection has also been found in human brain tissue.p2y12r density was negatively correlated with the distance between microglial membrane and neuronal membrane in the junction. in addition, more p2y12r on microglia membrane directly contacted the neuronal bodies. these results suggest that purinergic signals play an important role in the formation of neuronal somatic junctions in microglia. the researchers injected psb0739, a highly selective p2y12r inhibitor, into the cistern cerebellomedullary cistern significantly reduced the cell body connection life of microglia and neurons (about 45%), but did not affect the life span of microglia neuron dendrite contact. these results indicate that microglia sense neuronal activity through p2y12r signal. is there another possibility that microglia can directly feel the changes of neuronal activity? The virus carrying hsyn-hm3d (GQ) - mCherry was injected into the cortex of CX3CR1 GFP mice and cx3cr1-gfp-p2y12r knockout mice by chemical genetics technology. In this way, whether microglia could directly perceive the activity of neurons with or without p2y12r could be observed. The results showed that chronic activation of neuronal activity could promote the contact between microglia and cell bodies in CX3CR1 GFP mice, However, this effect was not observed in cx3cr1-gfp-p2y12r knockout mice. this further indicates that microglia perceive neuronal activity through p2y12r signal in this new connection site. these new connections are all in normal physiological state, so what function does this connection play in pathological state? Studies have shown that microglia respond rapidly to the changes of neuronal activity in the infarct border area after stroke. the researchers found broken mitochondrial structures in stroke mice, and the number of connections between microglia and neuronal bodies increased by about 3.8 times. however, p2y12r inhibitor psb0739 could block the increase of this connection. these results suggest that this new connection can protect neurons from damage under pathological conditions. in conclusion, we found that under normal physiological conditions, microglia and neurons in human and mouse form a new connection different from synapse, which depends on purinergic signal pathway, through which microglia can realize dynamic monitoring of neuronal state. references; Csaba, CSER é P, BAL á ZS P ó SFAI, Barbara Orsolits；Microglia monitor and protect neuronal function via specialized somatic purinergic junctions；Science 10.1126/ science.aax6752 (2019). 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