Neurotransmission is a key event in neuronal communication. It is initiated by fusion of neurotransmitter-filled synaptic vesicles with the presynaptic plasma membrane. To preserve the structural and molecular integrity of presynapse and to allow for sustained neurotransmission, the released vesicles are recycled to become available for the next round of exocytosis. This “synaptic vesicle cycle” is tightly controlled in space and time, which has important consequences for the plastic properties of presynapse. Recently, function in regulation of synaptic vesicle recycling and trafficking emerged for several proteins traditionally tightly linked to brain disease and, vice versa, mutations in well-known synaptic geneshave proven to be causal for neurological and neuropsychiatric conditions. Moreover, early defect in neurotransmission and presynaptic plasticity were reported in neurodegenerative diseases like Alzheimer’s, Parkinson’s or Huntington’s disease. These observations indicate that dysregulation of the complex membrane trafficking process, which mediate vesicle recycling at presynapse, might be the primary cause of dysfunction in several brain pathologies and, as such, also feasible entry point for new therapeutic strategies. In this symposium, we will address these new developments in four talks. Anna Fassio will introduce her work on synaptic genes (e.g. SYN1, TBC1D24, ATP6V1A and DMXL2) mutated in epilepsy, intellectual disability or autism and linked to aberrant synaptic endo/lysosomal trafficking. The second speaker, Silvio Rizzoli, will present his unique biochemical approach to address presynaptic proteostasis and its effect on vesicle recycling and synapse aging.Subhojit Roy will present his work on role of alpha-synuclein, which is tightly linked with pathology of Parkinson’s disease, in normal synaptic function. In the fifth talk Anna Fejtova will discuss the role of amyloid beta, its precursor protein, APP, and thereof derived fragments in the physiological regulation of neurotransmission. Student short talks given by RonjaAlica Angelika Göhde (Bergen, Norway) and Christos Galanis (Freiburg, Germany) will complement the symposium.

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