Dyszkant, N. | 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.

neuroscience↗

bioRxiv2024

Photoreceptor degeneration has heterogeneous effects on functional retinal ganglion cell types

Retinitis pigmentosa is a hereditary disease causing progressive degeneration of rod and cone photoreceptors, with no effective therapies. Using the rd10 mouse model, which mirrors the human condition, we examined its disease progression. Rods deteriorate by postnatal day (P) 45, followed by cone degeneration, with most photoreceptors lost by P180. Until then, retinal ganglion cells (RGCs) remain light-responsive, albeit only under photopic conditions, despite extensive outer retinal remodelling. However, it is still unknown whether the different functional RGC types remain stable, or if some types differentially alter their activity or are even lost during disease progression. Here, we addressed if and how the response diversity of functional RGC types changes with rd10 disease progression. At P30, we were able to identify all functional wild-type RGC types also in rd10 retina, suggesting that at this early degenerative stage, the full breadth of retinal output is still present. Remarkably, we found that the fractions of functional types changed throughout progressing degeneration between rd10 and wild-type: Responses of RGCs with Off-components ( Off and On-Off RGCs) seemed to be more vulnerable than On-cells, with Fast-On types being the most resilient. Notably, direction-selective RGCs appeared to be more vulnerable than orientation-selective RGCs. In summary, we found differences in resilience of response types (from resilient to vulnerable): Uncertain > Fast On > Slow On > On-Off > Off. Taken together, our results suggest that rd10 photoreceptor degeneration has heterogeneous effects on functional RGC types, with distinct sets of types losing their characteristic light responses earlier than others. This differential susceptibility of RGC circuits may be of relevance for future neuroprotective therapeutic strategies.

neuroscience↗