Schwerd-Kleine, T. | bioRxiv Science

bioRxiv2025

A large-scale dataset of functional mouse ganglion cell layer responses

We present the AO_SCPLOWLLC_SCPLOW-GCL dataset, a large-scale resource of functional two-photon Ca2+-imaging recordings with rich meta-data information from more than 80,000 cells in the ganglion cell layer (GCL) of the ex vivo mouse retina. Collected over nine years across more than 139 experimental sessions, the dataset provides recordings of light-evoked responses to various stimuli, including a shared set of core stimuli. To enable cell-type-specific analyses, cells are probabilistically assigned to 46 previously characterized functional groups, including retinal ganglion cells and displaced amacrine cells. Further, we assessed the influence of experimental and biological factors on the functional responses and found only small batch effects across experimenters, setups, and recording sessions, highlighting the datasets consistency. The AO_SCPLOWLLC_SCPLOW-GCL dataset offers a comprehensive and standardised reference for studying retinal computation at scale. It supports population-level analyses, computational modelling, and the development of machine learning approaches for biological time-series data. Future releases will expand the dataset with additional mouse lines and light stimuli, creating a growing resource for the vision science community.

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bioRxiv2023

Nitric oxide mediates differential effects in 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 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.

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