title: Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses.
abstract: Complexin (Cplx) proteins modulate the core SNARE complex to regulate exocytosis. To understand the contributions of Cplx to signaling in a well-characterized neural circuit, we investigated how Cplx3, a retina-specific paralog, shapes transmission at rod bipolar (RB)→AII amacrine cell synapses in the mouse retina. Knockout of Cplx3 strongly attenuated fast, phasic Ca(2+)-dependent transmission, dependent on local [Ca(2+)] nanodomains, but enhanced slower Ca(2+)-dependent transmission, dependent on global intraterminal [Ca(2+)] ([Ca(2+)]I). Surprisingly, coordinated multivesicular release persisted at Cplx3(-/-) synapses, although its onset was slowed. Light-dependent signaling at Cplx3(-/-) RB→AII synapses was sluggish, owing largely to increased asynchronous release at light offset. Consequently, propagation of RB output to retinal ganglion cells was suppressed dramatically. Our study links Cplx3 expression with synapse and circuit function in a specific retinal pathway and reveals a role for asynchronous release in circuit gain control.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Lena S
authors.initials: LS
authors.lastname: Mortensen
authors.affiliation: Department of Ophthalmology and Visual Science, Yale University, New Haven, CT 06511, USA.
authors.forename: Silvia J H
authors.initials: SJH
authors.lastname: Park
authors.affiliation: Department of Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Jiang-Bin
authors.initials: JB
authors.lastname: Ke
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Cooper
authors.affiliation: Department of Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Cordelia
authors.initials: C
authors.lastname: Imig
authors.affiliation: Department of Systems Neuroscience, Bernstein Focus Neurotechnology, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Siegrid
authors.initials: S
authors.lastname: Löwel
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Department of Ophthalmology and Visual Science, Yale University, New Haven, CT 06511, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06511, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Demb
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. Electronic address: rhee@em.mpg.de.
authors.forename: Jeong-Seop
authors.initials: JS
authors.lastname: Rhee
authors.affiliation: Department of Biology, University of Maryland, College Park, MD 20742, USA. Electronic address: jhsinger@umd.edu.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Singer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D005136:Eye Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D057146:Multivesicular Bodies / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C529624:Cplx3 protein, mouse; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D002118:Calcium