The researchers found the structural basis of synaptic steady-state regulation.

The decrease of postsynaptic glutamate receptor (pglur) can induce the increase of presynaptic neurotransmitter release to maintain synaptic transmission function, which is called synaptic homeostasis.how postsynaptic receptors reverse affect presynaptic structure and function across synapses is a core scientific problem in neurobiology.the disorder of synaptic structure and function is closely related to many kinds of neuropsychiatric diseases such as schizophrenia, autism and mental retardation. Analyzing how postsynaptic glutamate receptor regulates the changes of presynaptic structure and function can provide new ideas for the treatment of related diseases.little is known about the structural basis of synaptic homeostasis regulation.the Zhang Yongqing research group of the Institute of genetics and developmental biology, Chinese Academy of Sciences, and the rainfall intensity research group of the biological imaging platform center closely cooperated to analyze the structural changes of presynaptic homeostasis induced by the decrease of postsynaptic receptors using the Drosophila neuromuscular synapses as the model system.in wild-type Drosophila, there is an electron dense structure called T-bar in the neuromuscular synaptic active region.cytoskeleton protein BRP is the homologous protein of elks protein of mammalian cast / ERC family in Drosophila.it is a key component of T-bar structure, and the absence of BRP will lead to assembly defects of active region.super resolution microscopy showed that a single active region contained a single BRP ring.however, our team found that in the neuromuscular synapses of Drosophila melanogaster, when gluriic decreased, the plaque of presynaptic active region protein BRP staining increased. The super-resolution results showed that the increased BRP plaques were BRP polycyclic structure, and the electron microscope results showed that a single active region contained multiple T-bars.electrophysiological analysis showed that the microexcitatory potential intensity decreased but the presynaptic quantum release increased in the neuromuscular synapses of gluriic mutant, indicating that presynaptic steady-state regulation took place in gluriic mutant. At the same time, BRP multicyclic structure was also detected in the other two classical paradigms of presynaptic homeostasis, gluriia mutant and PHTx drug inhibition of glutamate receptor activity in neuromuscular synapses. The results suggest that the formation of BRP multicyclic structure in the active region may be the structural basis of presynaptic homeostasis regulation.studies over the past decade have shown that cell adhesion molecules play an important role in synaptic plasticity and synaptic structure specific assembly.neuroligin (NLG) is an important postsynaptic cell adhesion molecule, which connects with presynaptic neurexin (NRX) molecule and regulates the correct assembly of synaptic structure.there are four neuroligin coding genes in Drosophila, among which nlg1 has been studied more.through genetic manipulation, combined with ultra-high resolution microscopic imaging technology and electrophysiological technology, the team has proved that nlg1 is involved in the formation of BRP multicyclic structure during gluriic knockdown.this study reveals that the decrease of postsynaptic receptors leads to structural changes in the process of presynaptic homeostasis, and indicates that cell adhesion molecule nlg1 is involved in the formation of this structural change, which deepens the understanding of the regulation mechanism of presynaptic homeostasis.the study was published online on March 8 in the Journal of neuroscience（ DOI:10.1523/JNEUROSCI.2002-19.2020 )。 Hong Huilin, a doctoral student of Zhang Yongqing's research group, is the first author of the paper. the research was supported by the National Natural Science Foundation of China and the Ministry of science and technology. figures. Top: pre synaptic BRP aggregation in gluriicrnai and gluriichypo mutants forms BRP multicyclic structure; lower: mechanism model of presynaptic glutamate receptor reduction inducing presynaptic homeostasis to form multiple T-bar structures. Source: Institute of genetics and developmental biology, Chinese Academy of Sciences