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A novel approach to the functional classification of retinal ganglion cells

View ORCID ProfileGerrit Hilgen, Evgenia Kartsaki, View ORCID ProfileViktoriia Kartysh, Bruno Cessac, Evelyne Sernagor
doi: https://doi.org/10.1101/2021.05.09.443323
Gerrit Hilgen
1Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
2Health & Life Sciences, Applied Sciences, Northumbria University, Newcastle upon Tyne UK
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  • ORCID record for Gerrit Hilgen
  • For correspondence: gerrit.hilgen@northumbria.ac.uk evelyne.sernagor@ncl.ac.uk
Evgenia Kartsaki
1Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
3Université Côte d’Azur, Inria, Biovision team and Neuromod Institute, Sophia Antipolis Cedex, France
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Viktoriia Kartysh
1Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
4Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), 1090 Vienna, Austria
5Research Centre for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, 1090 Vienna, Austria
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Bruno Cessac
3Université Côte d’Azur, Inria, Biovision team and Neuromod Institute, Sophia Antipolis Cedex, France
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Evelyne Sernagor
1Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
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  • For correspondence: gerrit.hilgen@northumbria.ac.uk evelyne.sernagor@ncl.ac.uk
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Abstract

Retinal neurons come in remarkable diversity based on structure, function and genetic identity. Classifying these cells is a challenging task, requiring multimodal methodology. Here, we introduce a novel approach for retinal ganglion cell (RGC) classification, based on pharmacogenetics combined with immunohistochemistry and large-scale retinal electrophysiology. Our novel strategy allows grouping of cells sharing gene expression and understanding how these cell classes respond to basic and complex visual scenes. Our approach consists of increasing the firing level of RGCs co-expressing a certain gene (Scnn1a or Grik4) using excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and then correlate the location of these cells with post hoc immunostaining, to unequivocally characterize anatomical and functional features of these two groups. We grouped these isolated RGC responses into multiple clusters based on the similarity of the spike trains. With our approach, and accompanied by immunohistochemistry, we were able to extend the pre-existing list of Grik4 expressing RGC types to a total of 8 RGC types and, for the first time, we provide a phenotypical description of 14 Scnn1a-expressing RGCs. The insights and methods gained here can guide RGC classification but also neuronal classification challenges in other brain regions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 10, 2021.
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A novel approach to the functional classification of retinal ganglion cells
Gerrit Hilgen, Evgenia Kartsaki, Viktoriia Kartysh, Bruno Cessac, Evelyne Sernagor
bioRxiv 2021.05.09.443323; doi: https://doi.org/10.1101/2021.05.09.443323
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A novel approach to the functional classification of retinal ganglion cells
Gerrit Hilgen, Evgenia Kartsaki, Viktoriia Kartysh, Bruno Cessac, Evelyne Sernagor
bioRxiv 2021.05.09.443323; doi: https://doi.org/10.1101/2021.05.09.443323

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