Changes in glycinergic neurotransmission alter mammalian retinal information processing
Glycine, along with GABA, constitutes the major inhibitory neurotransmitter in the central nervous system. In the retina, glycinergic neurotransmission is primarily used by amacrine cells that are involved in the lateral processing of visual stimuli in the inner retina. We have previously shown that...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Molecular Neuroscience |
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| author | Anneka Joachimsthaler Anneka Joachimsthaler Katharina Hauf Katharina Hauf Anja Armbruster Shiri Zayit-Soudry Efrat Naaman Ido Perlman Rina Leibu Alina Kurolap Hagit Baris Feldman Hagit Baris Feldman Jan Kremers Jan Kremers Volker Eulenburg Volker Eulenburg Volker Eulenburg |
| author_facet | Anneka Joachimsthaler Anneka Joachimsthaler Katharina Hauf Katharina Hauf Anja Armbruster Shiri Zayit-Soudry Efrat Naaman Ido Perlman Rina Leibu Alina Kurolap Hagit Baris Feldman Hagit Baris Feldman Jan Kremers Jan Kremers Volker Eulenburg Volker Eulenburg Volker Eulenburg |
| author_sort | Anneka Joachimsthaler |
| collection | DOAJ |
| description | Glycine, along with GABA, constitutes the major inhibitory neurotransmitter in the central nervous system. In the retina, glycinergic neurotransmission is primarily used by amacrine cells that are involved in the lateral processing of visual stimuli in the inner retina. We have previously shown that the high-affinity glycine transporter 1 (GlyT1), that is commonly used as a reliable marker for glycinergic amacrine cells in the retina, is essential for glycinergic neurotransmission by these cells. Abolishment of retinal GlyT1 expression results in a breakdown of glycinergic neurotransmission by AII amacrine cells, but most likely also by other glycinergic amacrine cell populations. However, the impact of loss of glycinergic neurotransmission on retinal signal processing and visually guided behavior, has not yet been elucidated. In this study, the effects of loss of retinal GlyT1 expression in glycinergic amacrine cells on the optomotor reflex and on the photopic and scotopic electroretinogram (ERG) responses were analyzed. We show that retinal GlyT1-deficient mice have normal optomotor responses to rotating black and white stripes. When stimuli with sawtooth luminance profiles were used, thereby differentially activating ON and OFF pathways, the GlyT1 deficient mice showed facilitated responses to ON preferring stimuli, whereas responses to OFF preferring stimuli were unchanged. These findings were corroborated by ERG recordings that showed undistinguishable responses after flash stimulation but revealed differences in the differential processing of ON and OFF preferring stimuli. To determine if the function of retinal GlyT1 is conserved in humans, we analyzed ERG recordings from a patient diagnosed with GlyT1 encephalopathy. We show that GlyT1 deficiency results in marked ERG changes, characterized by an almost complete loss of the “photopic hill” phenomenon, a hill-like appearance of the relationship between the b-wave amplitude and log light stimulus strength under background illumination conditions, and reductions in the ERG oscillatory potentials in the dark- and light-adapted states. Both findings are consistent with an altered interaction between ON- and OFF pathways in the retina. Taken together our data show that glycinergic neurotransmission in the retina has important functions in retinal ON and OFF processing both in mice and humans. |
| format | Article |
| id | doaj-art-49e43164c4874a3f8904bd994cedd84f |
| institution | DOAJ |
| issn | 1662-5099 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-49e43164c4874a3f8904bd994cedd84f2025-08-20T02:56:12ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-05-011810.3389/fnmol.2025.15648701564870Changes in glycinergic neurotransmission alter mammalian retinal information processingAnneka Joachimsthaler0Anneka Joachimsthaler1Katharina Hauf2Katharina Hauf3Anja Armbruster4Shiri Zayit-Soudry5Efrat Naaman6Ido Perlman7Rina Leibu8Alina Kurolap9Hagit Baris Feldman10Hagit Baris Feldman11Jan Kremers12Jan Kremers13Volker Eulenburg14Volker Eulenburg15Volker Eulenburg16Department of Ophthalmology, University Hospital Erlangen, Erlangen, GermanyAnimal Physiology, Department of Biology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyDepartment of Biochemistry and Molecular Medicine, Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, GermanyDepartment of Anesthesiology and Intensive Care Therapy, University of Leipzig, Leipzig, GermanyDepartment of Biochemistry and Molecular Medicine, Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, GermanyDepartment of Ophthalmology, Rabin Medical Center, Petah Tikva, IsraelDepartment of Ophthalmology, Rabin Medical Center, Petah Tikva, IsraelThe Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, IsraelDepartment of Ophthalmology, Rambam Human Health Care Campus, Haifa, IsraelThe Genetics Institute and Genomic Center, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelThe Genetics Institute and Genomic Center, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelSchool of Medicine, Faculty for Medical & Health Sciences, Tel Aviv University, Tel Aviv, IsraelDepartment of Ophthalmology, University Hospital Erlangen, Erlangen, GermanyAnimal Physiology, Department of Biology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, GermanyDepartment of Biochemistry and Molecular Medicine, Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, GermanyDepartment of Anesthesiology and Intensive Care Therapy, University of Leipzig, Leipzig, Germany0Translational Anesthesiology and Intensive Care, Medical Faculty University of Augsburg, Augsburg, GermanyGlycine, along with GABA, constitutes the major inhibitory neurotransmitter in the central nervous system. In the retina, glycinergic neurotransmission is primarily used by amacrine cells that are involved in the lateral processing of visual stimuli in the inner retina. We have previously shown that the high-affinity glycine transporter 1 (GlyT1), that is commonly used as a reliable marker for glycinergic amacrine cells in the retina, is essential for glycinergic neurotransmission by these cells. Abolishment of retinal GlyT1 expression results in a breakdown of glycinergic neurotransmission by AII amacrine cells, but most likely also by other glycinergic amacrine cell populations. However, the impact of loss of glycinergic neurotransmission on retinal signal processing and visually guided behavior, has not yet been elucidated. In this study, the effects of loss of retinal GlyT1 expression in glycinergic amacrine cells on the optomotor reflex and on the photopic and scotopic electroretinogram (ERG) responses were analyzed. We show that retinal GlyT1-deficient mice have normal optomotor responses to rotating black and white stripes. When stimuli with sawtooth luminance profiles were used, thereby differentially activating ON and OFF pathways, the GlyT1 deficient mice showed facilitated responses to ON preferring stimuli, whereas responses to OFF preferring stimuli were unchanged. These findings were corroborated by ERG recordings that showed undistinguishable responses after flash stimulation but revealed differences in the differential processing of ON and OFF preferring stimuli. To determine if the function of retinal GlyT1 is conserved in humans, we analyzed ERG recordings from a patient diagnosed with GlyT1 encephalopathy. We show that GlyT1 deficiency results in marked ERG changes, characterized by an almost complete loss of the “photopic hill” phenomenon, a hill-like appearance of the relationship between the b-wave amplitude and log light stimulus strength under background illumination conditions, and reductions in the ERG oscillatory potentials in the dark- and light-adapted states. Both findings are consistent with an altered interaction between ON- and OFF pathways in the retina. Taken together our data show that glycinergic neurotransmission in the retina has important functions in retinal ON and OFF processing both in mice and humans.https://www.frontiersin.org/articles/10.3389/fnmol.2025.1564870/fullglycinesynaptic inhibitionretinaamacrine cellsERGON-OFF signalling |
| spellingShingle | Anneka Joachimsthaler Anneka Joachimsthaler Katharina Hauf Katharina Hauf Anja Armbruster Shiri Zayit-Soudry Efrat Naaman Ido Perlman Rina Leibu Alina Kurolap Hagit Baris Feldman Hagit Baris Feldman Jan Kremers Jan Kremers Volker Eulenburg Volker Eulenburg Volker Eulenburg Changes in glycinergic neurotransmission alter mammalian retinal information processing Frontiers in Molecular Neuroscience glycine synaptic inhibition retina amacrine cells ERG ON-OFF signalling |
| title | Changes in glycinergic neurotransmission alter mammalian retinal information processing |
| title_full | Changes in glycinergic neurotransmission alter mammalian retinal information processing |
| title_fullStr | Changes in glycinergic neurotransmission alter mammalian retinal information processing |
| title_full_unstemmed | Changes in glycinergic neurotransmission alter mammalian retinal information processing |
| title_short | Changes in glycinergic neurotransmission alter mammalian retinal information processing |
| title_sort | changes in glycinergic neurotransmission alter mammalian retinal information processing |
| topic | glycine synaptic inhibition retina amacrine cells ERG ON-OFF signalling |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2025.1564870/full |
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