Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Wednesday Speaker Abstracts

RELEASE SITE RECRUITMENT AND ACTIVATION AS MECHANISMS OF PRESYNAPTIC PLASTICITY Alexander M. Walter ; 1 Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany 2 Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany 3 University of Southern California, Department of Neurobiology, Los Angeles, California, USA 4 Institut für Neurophysiologie, Charité Universitätsmedizin, Berlin, Germany 5 Max Planck Institute for Biophysical Chemistry, Department of Nanobiophotonics, Gottingen, Baden-Württemberg, Germany 6 Buck Institute for Research on Aging, Novato, California, USA Neuronal communication across synapses relies on neurotransmitter release from presynaptic active zones (AZs) followed by postsynaptic transmitter detection. Synaptic plasticity homeostatically maintains functionality during perturbations and enables memory formation. Postsynaptic plasticity targets neurotransmitter receptors, but presynaptic mechanisms regulating the neurotransmitter release apparatus remain largely enigmatic. By studying Drosophila neuromuscular junctions (NMJs) we show that AZs consist of nano- modular release sites and identify a molecular sequence that adds modules within minutes of inducing homeostatic plasticity. This requires cognate transport machinery and specific AZ- scaffolding proteins. Structural remodeling is not required for immediate potentiation of neurotransmitter release, but necessary to sustain potentiation over longer timescales. Finally, mutations in Unc13 disrupting homeostatic plasticity at the NMJ also impair short-term memory when central neurons are targeted, suggesting that both plasticity mechanisms utilize Unc13. Together, while immediate synaptic potentiation capitalizes on available material, it triggers the coincident incorporation of modular release sites to consolidate synaptic potentiation.

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