Szatko, K. | 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

A metabotropic glutamate receptor agonist enhances visual signal fidelity in a mouse model of retinitis pigmentosa

Many inherited retinal diseases target photoreceptors, which transduce light into a neural signal that is processed by the downstream visual system. As photoreceptors degenerate, physiological and morphological changes to retinal synapses and circuitry reduce sensitivity and increase noise, degrading visual signal fidelity. Here, we pharmacologically targeted the first synapse in the retina in an effort to reduce circuit noise without sacrificing visual sensitivity. We tested a strategy to partially replace the neurotransmitter lost when photoreceptors die with an agonist of receptors that ON bipolars cells use to detect glutamate released from photoreceptors. In rd10 mice, which express a photoreceptor mutation that causes retinitis pigmentosa (RP), we found that a low dose of the mGluR6 agonist L-2-amino-4-phosphonobutyric acid (L-AP4) reduced pathological noise induced by photoreceptor degeneration. After making in vivo electroretinogram recordings in rd10 mice to characterize the developmental time course of visual signal degeneration, we examined effects of L-AP4 on sensitivity and circuit noise by recording in vitro light-evoked responses from individual retinal ganglion cells (RGCs). L-AP4 decreased circuit noise evident in RGC recordings without significantly reducing response amplitudes, an effect that persisted over the entire time course of rod photoreceptor degeneration. Subsequent in vitro recordings from rod bipolar cells (RBCs) showed that RBCs are more depolarized in rd10 retinas, likely contributing to downstream circuit noise and reduced synaptic gain, both of which appear to be ameliorated by hyperpolarizing RBCs with L-AP4. These beneficial effects may reduce pathological circuit remodeling and preserve the efficacy of therapies designed to restore vision. Significance StatementRetinitis Pigmentosa (RP) is an inherited degenerative disease that affects more than two million people worldwide. RP patients first lose peripheral and low-light vision due to the progressive death of their highly sensitive rod photoreceptors. Photoreceptor degeneration induces pathological noise within the retinal circuit, leading to dramatic structural changes that may hamper therapies to restore visual sensitivity. We discovered a pharmacological treatment that reduces pathological activity in a mouse model of RP without diminishing signaling in surviving circuitry. Partially replacing the neurotransmitter lost when photoreceptors die reduced noise in the retinal circuit without eliminating light sensitivity. This approach could limit the impact of the disease on retinal neurons and preserve the efficacy of subsequent restorative therapies.

neuroscience↗

bioRxiv2019

An arbitrary-spectrum spatial visual stimulator for vision research

Visual neuroscientists require accurate control of visual stimulation. However, few stimulator solutions simultaneously offer high spatio-temporal resolution and free control over the spectra of the light sources, because they rely on off-the-shelf technology developed for human trichromatic vision. Importantly, consumer displays fail to drive UV-shifted short wavelength-sensitive photoreceptors, which strongly contribute to visual behaviour in many animals, including mice, zebrafish and fruit flies. Moreover, many non-mammalian species feature more than three spectral photoreceptor types. Here, we present a flexible, spatial visual stimulator with up to 6 arbitrary spectrum chromatic channels. It combines a standard digital light processing engine with open source hard- and software that can be easily adapted to the experimentalists needs. We demonstrate the capability of this general visual stimulator experimentally in the in vitro mouse retinal whole-mount and the in vivo zebrafish. Hereby, we intend starting a community effort of sharing and developing a common stimulator design.

neuroscience↗