Researchers found out how structural changes at presynapses occur to promote increases at presynaptic release sites during homeostatic regulation, according to a recent study conducted by Prof. ZHANG Yongqing's group from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences.
Synaptic connections undergo homeostatic readjustment in response to changes of synaptic activity, to ensure a flexible yet stable nervous system. Compelling evidence has shown that homeostatic signaling acts in both the central and peripheral nervous systems in various species ranging from Drosophila to humans. Extensive studies have uncovered molecular mechanisms underlying this homeostatic regulation, but researchers have no idea whether the structural changes during this process.
To address this question, researchers constructed one mutant (GluRIIC mutant) which is significant reduction of GluRs firstly. Through electrophysiological examination, researchers confirmed that perturbing to postsynaptic GluRs triggered presynaptic neurotransmitter release increasing in this mutant. To explore the ultrastructure of synapses, they took advantage of super resolution microscopy to detect the structural of the key component of presynapse.
On the basis of early researches, the authors have known that active zone is a specialized structure of presynaptic release sites, which mediates neurotransmitter release and consists of an evolutionarily conserved protein complex. The cytoskeleton protein Brp is a key component of AZ. Super-resolution microscopy reveals a Brp ring at each AZ.
In this study, the researchers first found that multiple Brp rings by super resolution microscopy form at AZs of Drosophila NMJ when GluRs are reduced. To further confirm that multiple Brp rings are the structural basis for synaptic homeostasis, researchers subjected two classic homeostatic induction models. They found similar multiple Brp rings at individual AZs. Taken together, these data suggested that the formation of multiple Brp rings at AZs might be a structural basis for synaptic homeostasis.
Over the past decade, it has become increasingly apparent that synaptic cell adhesion molecules are critically involved in synapse plasticity and specication of synaptic properties. Neuroligin (Nlg), a member of the well characterized post-synaptic family of synaptic cell adhesion proteins. Researchers found that Nlg1 plays an important role during the formation of multiple Brp rings. Thus, this study reveals a novel role of Nlg1 for synaptic homeostasis.
Extensive recent studies in Drosophila and mammals demonstrate that structural reorganization of AZs is a conserved mechanism for modulating neurotransmission efficacy. This study uncovers the prominent multiple Brp ring structure at presynaptic terminals induced by homeostatic regulation is an important and well-conserved process. It will be of great interest to further clarify the functional implication of multiple Brp rings in synaptic homeostasis.
This study was supported by grants from the National Natural Science Foundation of China and Ministry of Science and Technology of China support plan.
Up panel, Multiple Brp rings cluster together in GluRIICRNAi and GluRIIChypo mutants. Down panel, Model describing the role of Nlg1/Nrx in controlling the formation of multiple T-bars at GluRIIC mutant NMJs. (Image by IGDB)
