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Voltage-gated calcium channel subunit α2δ-3 shapes light responses of mouse retinal ganglion cells mainly in low and moderate light levels

View ORCID ProfileHartwig Seitter, Vithiyanjali Sothilingam, Boris Benkner, Marina Garcia Garrido, Alexandra Kling, Antonella Pirone, View ORCID ProfileMathias Seeliger, View ORCID ProfileThomas A. Münch
doi: https://doi.org/10.1101/2020.02.10.941807
Hartwig Seitter
1Werner Reichardt Centre for Integrative Neuroscience (CIN) Otfried-Müller-Str. 25
5IMPRS for Cognitive and Systems Neuroscience Österbergstr. 3 Eberhard Karls Universität Tübingen 72076 Tübingen Germany
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  • ORCID record for Hartwig Seitter
Vithiyanjali Sothilingam
2Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 4/3
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Boris Benkner
1Werner Reichardt Centre for Integrative Neuroscience (CIN) Otfried-Müller-Str. 25
3Bernstein Center for Computational Neuroscience Otfried-Müller-Str. 25
5IMPRS for Cognitive and Systems Neuroscience Österbergstr. 3 Eberhard Karls Universität Tübingen 72076 Tübingen Germany
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Marina Garcia Garrido
2Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 4/3
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Alexandra Kling
1Werner Reichardt Centre for Integrative Neuroscience (CIN) Otfried-Müller-Str. 25
3Bernstein Center for Computational Neuroscience Otfried-Müller-Str. 25
5IMPRS for Cognitive and Systems Neuroscience Österbergstr. 3 Eberhard Karls Universität Tübingen 72076 Tübingen Germany
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Antonella Pirone
4Department of Otolaryngeology, Tübingen Hearing Research Center, Molecular Physiology of Hearing Elfriede-Aulhorn-Str. 5
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Mathias Seeliger
2Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 4/3
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  • ORCID record for Mathias Seeliger
Thomas A. Münch
1Werner Reichardt Centre for Integrative Neuroscience (CIN) Otfried-Müller-Str. 25
3Bernstein Center for Computational Neuroscience Otfried-Müller-Str. 25
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  • For correspondence: thomas.muench@cin.uni-tuebingen.de
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Abstract

Little is known about the function of the auxiliary α2δ subunits of voltage-gated calcium channels in the retina. We investigated the role of α2δ-3 (Cacna2d3) using a mouse in which α2δ-3 was knocked out by LacZ insertion. Behavior experiments indicated a normal optokinetic reflex in α2δ-3 knockout animals. Strong expression of α2δ-3 could be localized to horizontal cells using the LacZ-reporter, but horizontal cell mosaic and currents carried by horizontal cell voltage-gated calcium channels were unchanged by the α2δ-3 knockout. In vivo electroretinography revealed unaffected photoreceptor activity and signal transmission to depolarizing bipolar cells. We recorded visual responses of retinal ganglion cells with multi-electrode arrays in scotopic to photopic luminance levels and found subtle changes in α2δ-3 knockout retinas. Spontaneous activity in OFF ganglion cells was elevated in all luminance levels. Differential response strength to high- and low-contrast Gaussian white noise was compressed in ON ganglion cells during mesopic ambient luminance and in OFF ganglion cells during scotopic and mesopic ambient luminances. In a subset of ON ganglion cells, we found a sharp increase in baseline spiking after the presentation of drifting gratings in scotopic luminance. This increase happened after gratings of different spatial properties in knockout compared to wild type retinas. In a subset of ON ganglion cells of the α2δ-3 knockout, we found altered delays in rebound-like spiking to full-field contrast steps in scotopic luminance. In conclusion, α2δ-3 seems to participate in shaping visual responses mostly within brightness regimes when rods or both rods and cones are active.

Footnotes

  • ↵* current affiliations pending updates

  • Support or grant information: The study was supported by funds from the Werner-Reichardt Centre for Integrative Neuroscience Tübingen (CIN, DFG EXC 307) and the Bernstein Center for Computational Neuroscience Tübingen (BMBF, FKZ 01GQ1002).

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Posted February 11, 2020.
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Voltage-gated calcium channel subunit α2δ-3 shapes light responses of mouse retinal ganglion cells mainly in low and moderate light levels
Hartwig Seitter, Vithiyanjali Sothilingam, Boris Benkner, Marina Garcia Garrido, Alexandra Kling, Antonella Pirone, Mathias Seeliger, Thomas A. Münch
bioRxiv 2020.02.10.941807; doi: https://doi.org/10.1101/2020.02.10.941807
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Voltage-gated calcium channel subunit α2δ-3 shapes light responses of mouse retinal ganglion cells mainly in low and moderate light levels
Hartwig Seitter, Vithiyanjali Sothilingam, Boris Benkner, Marina Garcia Garrido, Alexandra Kling, Antonella Pirone, Mathias Seeliger, Thomas A. Münch
bioRxiv 2020.02.10.941807; doi: https://doi.org/10.1101/2020.02.10.941807

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