Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses

• Published in: Cell reports (Cambridge) Vol. 15; no. 10; pp. 2239 - 2250
• Main Authors: Mortensen, Lena S., Park, Silvia J.H., Ke, Jiang-bin, Cooper, Benjamin H., Zhang, Lei, Imig, Cordelia, Löwel, Siegrid, Reim, Kerstin, Brose, Nils, Demb, Jonathan B., Rhee, Jeong-Seop, Singer, Joshua H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.06.2016; Elsevier
• Subjects: Animals; Calcium - pharmacology; Exocytosis - drug effects; Eye Proteins - metabolism; Mice, Inbred C57BL; Multivesicular Bodies - drug effects; Multivesicular Bodies - metabolism; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - metabolism; Retina - cytology; Retina - drug effects; Retina - metabolism; Retinal Bipolar Cells - drug effects; Retinal Bipolar Cells - metabolism; Signal Transduction - drug effects; Synapses - drug effects; Synapses - metabolism; Synaptic Transmission - drug effects
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.05.012

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. [Display omitted] •Cplx3 boosts fast phasic transmitter release while suppressing asynchronous release•Transmission at rod bipolar cell ribbon synapses is sluggish in absence of Cplx3•Sustained depolarization of postsynaptic interneurons degrades light-evoked signaling Mortensen et al. link complexin-3-dependent synaptic dynamics at rod bipolar cell ribbon synapses to downstream retinal circuit function during rod-mediated vision. In the absence of complexin 3, enhanced asynchronous release from rod bipolar cells depolarizes the postsynaptic network and hinders transmission at synapses onto retinal ganglion cells.