Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses
Lena S. Mortensen,
Silvia J.H. Park,
Jiang-bin Ke,
Benjamin H. Cooper,
Lei Zhang,
Cordelia Imig,
Siegrid Löwel,
Kerstin Reim,
Nils Brose,
Jonathan B. Demb,
Jeong-Seop Rhee,
Joshua H. Singer
Affiliations
Lena S. Mortensen
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Silvia J.H. Park
Department of Ophthalmology and Visual Science, Yale University, New Haven, CT 06511, USA
Jiang-bin Ke
Department of Biology, University of Maryland, College Park, MD 20742, USA
Benjamin H. Cooper
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Lei Zhang
Department of Biology, University of Maryland, College Park, MD 20742, USA
Cordelia Imig
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Siegrid Löwel
Department of Systems Neuroscience, Bernstein Focus Neurotechnology, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, University of Göttingen, 37075 Göttingen, Germany
Kerstin Reim
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Nils Brose
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Jonathan B. Demb
Department of Ophthalmology and Visual Science, Yale University, New Haven, CT 06511, USA
Jeong-Seop Rhee
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Joshua H. Singer
Department of Biology, University of Maryland, College Park, MD 20742, USA
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 Ca2+-dependent transmission, dependent on local [Ca2+] nanodomains, but enhanced slower Ca2+-dependent transmission, dependent on global intraterminal [Ca2+] ([Ca2+]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.
