Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells
Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light a...
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/98742 |
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| author | Dominic Gonschorek Matías A Goldin Jonathan Oesterle Tom Schwerd-Kleine Ryan Arlinghaus Zhijian Zhao Timm Schubert Olivier Marre Thomas Euler |
| author_facet | Dominic Gonschorek Matías A Goldin Jonathan Oesterle Tom Schwerd-Kleine Ryan Arlinghaus Zhijian Zhao Timm Schubert Olivier Marre Thomas Euler |
| author_sort | Dominic Gonschorek |
| collection | DOAJ |
| description | Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca2+ imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina. This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level. Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields. Given that under photopic conditions, NO release is triggered by quick changes in light levels, we propose that these RGC types signal fast contrast changes to higher visual regions. Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+ imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO. By employing a sequential-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations. Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs. |
| format | Article |
| id | doaj-art-7ca3dea4f0114402ad72e3ea3383db7e |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-7ca3dea4f0114402ad72e3ea3383db7e2025-01-09T12:37:06ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.98742Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cellsDominic Gonschorek0https://orcid.org/0000-0001-5118-9817Matías A Goldin1Jonathan Oesterle2https://orcid.org/0000-0001-8919-1445Tom Schwerd-Kleine3Ryan Arlinghaus4Zhijian Zhao5https://orcid.org/0000-0002-3302-1495Timm Schubert6Olivier Marre7Thomas Euler8https://orcid.org/0000-0002-4567-6966Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany; GRK 2381 ’cGMP: From Bedside to Bench’, University of Tübingen, Tübingen, GermanyInstitut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, FranceWerner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany; Hertie Institute for AI in Brain Health, Tübingen AI Center, University of Tübingen, Tübingen, GermanyWerner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany; GRK 2381 ’cGMP: From Bedside to Bench’, University of Tübingen, Tübingen, GermanyWerner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, University of Tübingen, Tübingen, GermanyInstitute for Ophthalmic Research, University of Tübingen, Tübingen, GermanyWerner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, University of Tübingen, Tübingen, GermanyInstitut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, FranceWerner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany; GRK 2381 ’cGMP: From Bedside to Bench’, University of Tübingen, Tübingen, Germany; Bernstein Center for Computational Neuroscience, University of Tübingen, Tübingen, GermanyNeuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca2+ imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina. This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level. Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields. Given that under photopic conditions, NO release is triggered by quick changes in light levels, we propose that these RGC types signal fast contrast changes to higher visual regions. Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+ imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO. By employing a sequential-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations. Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs.https://elifesciences.org/articles/98742retinaneuromodulationnitric oxideganglion cells |
| spellingShingle | Dominic Gonschorek Matías A Goldin Jonathan Oesterle Tom Schwerd-Kleine Ryan Arlinghaus Zhijian Zhao Timm Schubert Olivier Marre Thomas Euler Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells eLife retina neuromodulation nitric oxide ganglion cells |
| title | Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells |
| title_full | Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells |
| title_fullStr | Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells |
| title_full_unstemmed | Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells |
| title_short | Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells |
| title_sort | nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells |
| topic | retina neuromodulation nitric oxide ganglion cells |
| url | https://elifesciences.org/articles/98742 |
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