title: Uniquantal release through a dynamic fusion pore is a candidate mechanism of hair cell exocytosis.
abstract: The mechanisms underlying the large amplitudes and heterogeneity of excitatory postsynaptic currents (EPSCs) at inner hair cell (IHC) ribbon synapses are unknown. Based on electrophysiology, electron and superresolution light microscopy, and modeling, we propose that uniquantal exocytosis shaped by a dynamic fusion pore is a candidate neurotransmitter release mechanism in IHCs. Modeling indicated that the extended postsynaptic AMPA receptor clusters enable large uniquantal EPSCs. Recorded multiphasic EPSCs were triggered by similar glutamate amounts as monophasic ones and were consistent with progressive vesicle emptying during pore flickering. The fraction of multiphasic EPSCs decreased in absence of Ca(2+) influx and upon application of the Ca(2+) channel modulator BayK8644. Our experiments and modeling did not support the two most popular multiquantal release interpretations of EPSC heterogeneity: (1) Ca(2+)-synchronized exocytosis of multiple vesicles and (2) compound exocytosis fueled by vesicle-to-vesicle fusion. We propose that IHC synapses efficiently use uniquantal glutamate release for achieving high information transmission rates.
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Bernstein Center for Computational Neuroscience, University of Göttingen, 37073 Göttingen, Germany; Max Planck Institute for Dynamics and Self-Organization, 37077 Göttingen, Germany.
authors.forename: Nikolai M
authors.initials: NM
authors.lastname: Chapochnikov
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama 359-8555, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takago
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Collaborative Research Center 889 Cellular Mechanisms of Sensory Processing, 37099 Göttingen, Germany.
authors.forename: Chao-Hua
authors.initials: CH
authors.lastname: Huang
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Collaborative Research Center 889 Cellular Mechanisms of Sensory Processing, 37099 Göttingen, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Pangršič
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Darina
authors.initials: D
authors.lastname: Khimich
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Collaborative Research Center 889 Cellular Mechanisms of Sensory Processing, 37099 Göttingen, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Neef
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Molecular Architecture of Synapses Junior Research Group, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Auge
authors.affiliation: Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Göttfert
authors.affiliation: Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University of Göttingen, 37073 Göttingen, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Hell
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Collaborative Research Center 889 Cellular Mechanisms of Sensory Processing, 37099 Göttingen, Germany; Molecular Architecture of Synapses Junior Research Group, University Medical Center Göttingen, 37075 Göttingen, Germany. Electronic address: cwichma@gwdg.de.
authors.forename: Carolin
authors.initials: C
authors.lastname: Wichmann
authors.affiliation: Bernstein Center for Computational Neuroscience, University of Göttingen, 37073 Göttingen, Germany; Max Planck Institute for Dynamics and Self-Organization, 37077 Göttingen, Germany; Collaborative Research Center 889 Cellular Mechanisms of Sensory Processing, 37099 Göttingen, Germany. Electronic address: fred@nld.ds.mpg.de.
authors.forename: Fred
authors.initials: F
authors.lastname: Wolf
authors.affiliation: InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37075 Göttingen, Germany; Bernstein Center for Computational Neuroscience, University of Göttingen, 37073 Göttingen, Germany; Collaborative Research Center 889 Cellular Mechanisms of Sensory Processing, 37099 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University of Göttingen, 37073 Göttingen, Germany. Electronic address: tmoser@gwdg.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D008962:Models, Theoretical; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents