报告摘要：

　　The process of synaptic vesicle priming is an essential determinant of the function, strength, and plasticity of nerve cell synapses, because it maintains a pool of readily releasable vesicles at any given time and determines the time course of synaptic fatigue and recovery. The corresponding forms of synaptic short-term plasticity determine multiple complex brain functions, from sensory adaptation to working memory. Munc13s execute synaptic vesicle priming by regulating the assembly of fusogenic SNARE complexes. They are themselves regulated by three major pathways, involving calcium-calmodulin signalling, diacylglycerol signalling, and calcium-phospholipid signalling. We studied the functional relevance of these regulatory pathways in various synapse types and found that calcium-dependent Munc13-regulating pathways are key determinants of synaptic short-term plasticity, synapse endurance, synaptic fidelity, and working memory. I will discuss these finding in the context of (i) the role of parallel signalling pathways targeting presynaptic function, (ii) the role of Munc13 priming proteins in determining the unique features of synaptic transmission, and (iii) the role of these processes in normal circuit function and a novel neurodevelopmental syndrome caused by pathogenic Munc13 variants.

报告人简介：

　　Nils Brose is a trained biochemist whose work focuses on molecular and cellular neurobiology. Born in Marburg (DE) in 1962, he studied biochemistry at the University of Tübingen (DE) and earned an MSc in physiology from the University of Oxford (UK) in 1987. He completed his doctorate in biology at Ludwig Maximilians University Munich (DE) in 1990 before undertaking postdoctoral research at the Salk Institute in San Diego (US) and the University of Texas Southwestern Medical Center in Dallas (US). In 1995, Nils Brose joined the Max Planck Institute of Experimental Medicine in Göttingen (DE) as a research group leader and Heisenberg Fellow. Since 2001, he has served as a Director of the institute's Department of Molecular Neurobiology, continuing this role following the 2022 merger that created the Max Planck Institute for Multidisciplinary Sciences. He was elected to the German National Academy of Sciences in 2014. Brose's laboratory investigates the molecular mechanisms underlying synapse formation, neurotransmitter release, and synaptic plasticity—the processes that enable neurons to transmit information and adapt during learning and development. His work on synaptic proteins has provided key insights into the mechanisms of synaptic communication and the biological basis of 'synaptopathies', i.e. neurological and neuropsychiatric disorders caused by synapse dysfunction.