Project Summary Synapses are key elements of communication and signal processing in the healthy brain. Furthermore, synapses are severely perturbed in several neurological and psychiatric diseases. This proposal requests support for an international scientific meeting on Synaptic Transmission as part of the Gordon Research Conference (GRC) series to be held at the Renaissance Tuscany Il Ciocco in Barga, Italy. This GRC will be preceded by a Gordon Research Seminar (GRS) targeted towards graduate students and post-doctoral fellows on June 20-21 at the same location. We will bring together scientists who all are highly interested in synaptic function but examine synapses at different levels (molecular, cellular, and systems level), look at them from different perspectives (bottom-up, top-down), and use different approaches (molecular biology, super-resolution imaging, 3D and cryo-electron microscopy, optogenetics, subcellular electrophysiology, modeling, and many others). The long-term objectives of the conference series are (1) to increase understanding of the fundamental molecular and cellular mechanisms of synaptic transmission, (2) to elucidate how synaptic transmission shapes neuronal network activity, and (3) to link basic science on synapses to understanding disease processes. We propose to build on the highly successful strategy of this traditional conference as well as implement innovative strategies for identifying and supporting under- represented minorities, and engaging trainees and established scientists using a mentor-mentee program. Thirty committed speakers will represent critical areas of synaptic transmission research for ~150 participants for an intense five-day conference in a retreat-like setting in Barga, Italy. The program will begin with a plenary session from a leader in the field, Guo-Ping Feng, who will talk about using transgenic marmosets to study synaptic dysfunction related to autism. Eight sessions will then address synaptic transmission from both pre- and postsynaptic perspectives including: structure, plasticity, signaling, artificial synaptic networks, pathology, relationships to perisynaptic astroglia, and the function of synapses in complex systems. Short talks and evening poster sessions on all four days will permit broad participation by trainees and junior faculty members. The final plenary talk will be given by Rob Malenka, a leader in studying synaptic plasticity who has focused on drug addiction. The health and disease relevance of this application is substantial. Although many presentations will focus on basic science, the data have far- reaching implications for devastating brain disorders that are emerging as synaptopathies including neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, mood disorders, schizophrenia, autism spectrum disorders, mental retardation, and drug addiction. The 2020 Synaptic Transmission GRC will have a major influence shaping both basic and disease-relate...