title: Miniature neurotransmission regulates Drosophila synaptic structural maturation.
abstract: Miniature neurotransmission is the transsynaptic process where single synaptic vesicles spontaneously released from presynaptic neurons induce miniature postsynaptic potentials. Since their discovery over 60 years ago, miniature events have been found at every chemical synapse studied. However, the in vivo necessity for these small-amplitude events has remained enigmatic. Here, we show that miniature neurotransmission is required for the normal structural maturation of Drosophila glutamatergic synapses in a developmental role that is not shared by evoked neurotransmission. Conversely, we find that increasing miniature events is sufficient to induce synaptic terminal growth. We show that miniature neurotransmission acts locally at terminals to regulate synapse maturation via a Trio guanine nucleotide exchange factor (GEF) and Rac1 GTPase molecular signaling pathway. Our results establish that miniature neurotransmission, a universal but often-overlooked feature of synapses, has unique and essential functions in vivo.
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Ben Jiwon
authors.initials: BJ
authors.lastname: Choi
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Imlach
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiao
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK.
authors.forename: Verena
authors.initials: V
authors.lastname: Wolfram
authors.affiliation: Department of Cellular and Molecular Physiology, Department of Genetics, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Grbic
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cela
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Baines
authors.affiliation: Department of Cellular and Molecular Physiology, Department of Genetics, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Nitabach
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: brian@mccabelab.org.
authors.forename: Brian D
authors.initials: BD
authors.lastname: McCabe
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D055369:Miniature Postsynaptic Potentials / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000502:physiology*