September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The absence of complexin 3 alters rod bipolar cell pathway function
Author Affiliations & Notes
  • Joshua H Singer
    Biology, University of Maryland, College Park, Maryland, United States
  • Lena S Mortensen
    AG Synapse Physiology, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
  • Silvia Jee Hyun Park
    Ophthalmology, Yale University, New Haven, Connecticut, United States
  • Jiang-bin Ke
    Biology, University of Maryland, College Park, Maryland, United States
  • Lei Zhang
    Biology, University of Maryland, College Park, Maryland, United States
  • Nils Brose
    AG Synapse Physiology, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
  • Jeong-Seop Rhee
    AG Synapse Physiology, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
  • Jonathan B Demb
    Ophthalmology, Yale University, New Haven, Connecticut, United States
    Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States
  • Footnotes
    Commercial Relationships   Joshua Singer, None; Lena Mortensen, None; Silvia Park, None; Jiang-bin Ke, None; Lei Zhang, None; Nils Brose, None; Jeong-Seop Rhee, None; Jonathan Demb, None
  • Footnotes
    Support  NIH Grant EY107836 to JHS; NIH Grant EY021372 to JBD and JHS; DFG Grant SFB889 to LSM, NB and JSR
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Joshua H Singer, Lena S Mortensen, Silvia Jee Hyun Park, Jiang-bin Ke, Lei Zhang, Nils Brose, Jeong-Seop Rhee, Jonathan B Demb; The absence of complexin 3 alters rod bipolar cell pathway function. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Complexins (cplx) regulate exocytosis by modulating the SNARE complex. A retina-specific cplx isoform, cplx3, is found in two neurons—rod bipolar (RB) and AII amacrine cells—in the circuit mediating night vision. We investigated the role of cplx3 in scotopic signal encoding by RB→AII synapses in the mouse retina.

Methods : Cplx3 knockout (cplx3-/-) mice and detailed methods are published (Xue et al. 2008; Ke et al. 2014). Retinas from littermate cplx3-/- and cplx3+/+ mice (either sex, P35-50) were used. We assessed transmission at RB→AII synapses by paired voltage-clamp recording of RBs and AIIs in light-adapted slices (200 µm) prepared from all areas of the retina. We made voltage- and current-clamp recordings from AIIs and ON α ganglion cells (GCs) in dark-adapted whole-mount preparations of the ventral retina to assess neural responses to light stimulation.

Results : Cplx3-/- attenuated phasic Ca2+-dependent transmission (~3-fold reduction; P < <0.01) and moderately enhanced Ca2+-independent spontaneous exocytosis (~2-fold increase; P << 0.01) without affecting vesicle recycling and, surprisingly, coordinated multivesicular release (MVR). We evaluated retinal circuit function in rod-mediated vision and found that cplx3-/- slowed both the rise and decay of responses to changes in full-field contrast at RB→AII synapses. Consequently, contrast-evoked changes in AII VM were slowed and reduced in amplitude, and propagation of RB output to ON α GCs via cone bipolar (CB) cells was inhibited dramatically: contrast-evoked excitatory currents recorded in ON α GCs were reduced in amplitude and slowed by cplx3-/-. Control experiments demonstrated that ON α GCs' responses to cone stimulation in cplx3-/- were fast and transient, similar to cplx3+/+, indicating that transmission at ON CB→ON α GC synapses was unaffected in cplx3-/-.

Conclusions : Inhibition of phasic release at RB→AII synapses in cplx3-/- resulted from the absence of a facilitatory effect of cplx3 on Ca2+-dependent exocytosis rather than from a depletion of the RRP by enhanced spontaneous release. The persistence of MVR in cplx3-/- provided insight into underlying mechanisms. Cplx3-/- prevented RB→AII synapses from encoding contrast in rapid changes in release rate; this defect altered signaling to downstream ON α GCs. Our study links changes in synapse and circuit function and reveals a role for spontaneous release in the regulation of circuit gain control.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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