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Published on: November 11, 2017
The absence of Complexin 3 and Complexin 4 differentially impacts the ON and OFF pathways in mouse retina
Immanuel Landgraf1, Johanna Mühlhans, Karin Dedek
1Department of Biology and Environmental Sciences, Neurobiology, University of Oldenburg, 26111 Oldenburg, Germany.
Abstract:
Complexins (Cplxs) regulate the speed and Ca(2+)-sensitivity of synaptic vesicle fusion. It has been shown that all four known Cplxs are present at mouse retinal synapses--at conventional amacrine cell synapses (Cplx 1 to Cplx 3) and at photoreceptor and bipolar cell ribbon synapses (Cplx 3 and Cplx 4) [K. Reim et al. (2005) J. Cell Biol., 169, 669-680]. Electroretinographic recordings in Cplx 3/Cplx 4 double-knockout (DKO) mice showed perturbed transmission in the outer plexiform layer, and possible changes in the inner plexiform layer [K. Reim et al. (2009) J. Cell Sci., 122, 1352-1361]. In the present study, we examined the effects of the absence of Cplx 3 and Cplx 4 on ganglion cell responses. We report that the lack of Cplx 3 and Cplx 4 differentially impacts the ON and OFF pathways. Under photopic conditions, the responses in the cone OFF pathway are largely unaffected, whereas the responses in the cone ON pathway are diminished in Cplx 3/Cplx 4 DKO mice. Under scotopic conditions, both ON and OFF response rates are reduced and high-sensitivity OFF responses are missing in Cplx 3/Cplx 4 DKO mice. The electrophysiological findings are corroborated by new immunocytochemical findings. We now show that rod spherules contain only Cplx 4. However, both Cplx 3 and Cplx 4 co-localize in cone pedicles. In the inner plexiform layer, Cplx 3 is present in rod bipolar cell terminals and in amacrine cell processes. Most importantly, Cplx 3 is localized in the lobular appendages of AII amacrine cells, the sites of signal transmission from the primary rod pathway into the OFF pathway in the inner plexiform layer.
Insights
Complexins 3 and 4 (Cplx 3/4) are crucial for retinal signal processing. Their absence differentially affects ON and OFF visual pathways, with significant impacts on scotopic vision and cone ON pathway responses.
Area of Science:
- Neuroscience
- Molecular Biology
- Vision Science
Background:
- Complexins (Cplxs) are key regulators of synaptic vesicle fusion.
- All four known Cplxs are found in mouse retinal synapses.
- Previous studies indicated perturbed retinal transmission in Cplx 3/Cplx 4 double-knockout (DKO) mice.
Purpose of the Study:
- To investigate the impact of Cplx 3 and Cplx 4 absence on retinal ganglion cell responses.
- To elucidate the specific roles of Cplx 3 and Cplx 4 in the ON and OFF visual pathways.
Main Methods:
- Electroretinography was used to record ganglion cell responses in Cplx 3/Cplx 4 DKO mice.
- Immunocytochemistry was employed to determine the localization of Cplx 3 and Cplx 4 in retinal synapses.
Main Results:
- The absence of Cplx 3 and Cplx 4 differentially affected ON and OFF pathways.
- Cone OFF pathway responses were largely unaffected under photopic conditions.
- Cone ON pathway responses were diminished in Cplx 3/Cplx 4 DKO mice.
- Scotopic ON and OFF response rates were reduced, and high-sensitivity OFF responses were absent.
- Rod spherules exclusively contain Cplx 4, while cone pedicles co-express Cplx 3 and Cplx 4.
- Cplx 3 is localized in rod bipolar cell terminals and AII amacrine cell processes.
Conclusions:
- Cplx 3 and Cplx 4 play distinct and essential roles in both photopic and scotopic vision.
- The findings highlight the differential contribution of Cplx 3 and Cplx 4 to the ON and OFF pathways in the retina.
