Biology subjects

Rodgers, J.

Publications and source records attributed to Rodgers, J..

11 recordsLinked to original sources

bioRxiv2026

Parallel visual processing in the suprachiasmatic region of a diurnal mammal.

Light shapes mammalian physiology and behaviour through hypothalamic pathways, yet how these pathways process visual information in day-active species remains poorly understood. Based largely on work in nocturnal rodents, the suprachiasmatic nucleus (SCN) is classically viewed as a retinal target that encodes ambient illumination for circadian entrainment. We combine anatomical tracing, light-evoked c-Fos mapping and high-density silicon-probe electrophysiology to define visual processing in the suprachiasmatic region of the diurnal murid Rhabdomys pumilio. We find that retinal input and light-evoked activity extend beyond the SCN into rostral and lateral peri-SCN hypothalamus. Within the SCN, neurons encode irradiance with graded changes in maintained firing broadly similar to those observed in parallel recordings of nocturnal Mus domesticus. Across the wider suprachiasmatic region, Rhabdomys neurons show selectivity for more dynamic visual stimuli, including luminance transitions, contrast and temporal structure. Unsupervised clustering identifies five functionally distinct hypothalamic visual response classes with different anatomical distributions. These findings reveal an expanded hypothalamic visual network in a diurnal mammal, placing SCN irradiance coding within a broader system for processing dynamic visual features.

neuroscience↗

bioRxiv2026

Circadian phase reconfigures information transmission in the mouse visual thalamus

Circadian clocks are a ubiquitous feature of the mammalian brain, yet whether they regulate how neural circuits encode and transmit information remains largely unknown. Here, we address this question in the mouse visual thalamus (dLGN), a key relay between retina and cortex that provides a tractable model for studying sensory information transfer. Using wireless electrophysiological recordings from awake, behaving mice, we show that spontaneous dLGN activity is under circadian control, peaking during the late subjective day. Combining visual stimulation, information-theoretic analyses, and optogenetic interrogation of retinogeniculate transmission, we demonstrate that circadian phase selectively reconfigures the visual code. Although fundamental tuning properties remain largely stable, the impact of circadian phase on information transfer depends on visual scene statistics, promoting a more efficient coding strategy at night under high-contrast conditions. Together, these findings identify circadian clocks as dynamic regulators of neuronal communication that actively reshape sensory information processing across the day-night cycle.

neuroscience↗

bioRxiv2026

Population analysis and host-disease associations of Shiga toxin-producing Escherichia coli from various sources across eleven European countries using whole genome sequencing

Shiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens, able to cause severe disease in humans. In the DiSCoVeR project (https://onehealthejp.eu/jrp-discover/) a STEC inventory from human and non-human sources from 11 European countries was set up and [≥] 3500 strains were sequenced to perform comparative genomics analysis. We used this dataset to assess STEC population structure and to investigate potential associations between genomic features, host reservoirs and symptoms. Most STEC isolates analysed by Whole Genome Sequencing (WGS) in this study were collected between years 2010-2020. An ad hoc pipeline was deployed for a harmonised characterization of the STEC in the database, allowing the determination of serotyping, stx gene subtyping, 7-loci MLST, virulotyping and cgMLST. The results were analysed with Principal Component Analysis (PCoA) in relation with isolation source to assess clustering of STEC subpopulations. When human STEC data were analysed, the PCoA revealed three distinct human STEC subpopulations (STEC_1, STEC_2 and STEC_3), which were further analysed for associations between genomic features, symptoms and variance. The non-human STEC showed a more dispersed distribution, except for one subpopulation with genes linked to specific host species, and some virulence profiles overlapping with the STEC_1 population. In conclusion, our analysis identified distinct STEC subpopulations from human cases, each characterized by specific genetic features and associated with varying proportions of severe disease outcomes. These findings provide novel insights supporting the risk assessment of STEC. Impact statement[This lay summary of your article should be no more than 200 words, and should a) provide a perspective of how this article adds to the literature in the field; b) identify breadth of interest/utility; and c) state the significance of output (incremental or step), in terms of relevance.] This study is based on the establishment of a One Health STEC genomes database, including sequences from isolates of different sources. Most of the isolates had been isolated in the ten-years time span 2010-2020, in 11 different countries, for surveillance and monitoring activities or specific surveys and research purposes. The final dataset included the whole genome sequencing of 3,418 STEC isolates, mainly from human cases of infections. The metadata included the host symptoms, where available, for human STEC strains and the animal source the strains had been isolated from. We set up a pipeline for the harmonized analysis of STEC WGS, called Discover, made available though ARIES webserver or GitHub. The analysis allowed a deep characterization of STEC strains circulating in Europe. We used this resource to assess STEC population structure and to investigate potential associations between genomic features, host reservoirs, and various symptoms associated with STEC infection by PCoA. This analysis highlighted the presence of subpopulation of human STEC associated with specific features. We provide new information useful for risk characterization, as well as a large dataset genome database and associated metadata compiled from STEC strains, representing a valuable resource for the scientific community, enabling further investigations into STEC diversity, evolution, source attribution and public health relevance. Data summaryThe authors confirm all supporting data, including sequence data accession numbers, code and protocols have been provided within the article or through supplementary data files. One supplementary method and five supplementary tables are available with the online version of this article

genomics↗

bioRxiv2024

Interaction between native and prosthetic visual responses in optogenetic visual restoration

Degenerative retinal disorders leading to irreversible photoreceptor death are a common cause of blindness. Optogenetic gene therapy aims to restore vision in affected individuals by introducing light sensitive opsins into the surviving neurons of inner retina. While up until now the main focus of optogenetic therapy has been on terminally blind individuals, treating at stages where residual native vision is present could have several advantages. Yet, it is still unknown how residual native and optogenetic vision would interact if present at the same time. Using transgenic mice expressing the optogenetic tool ReaChR in ON-bipolar cells, we herein examine this interaction through electroretinography (ERG) and visually evoked potentials (VEP). We find that optogenetic responses show a peculiar ERG signature and are enhanced in retinas without photoreceptor loss. Conversely, native responses are dampened in the presence of ReaChR. Moreover, in VEP recordings we find that optogenetic responses reach the cortex asynchronous to the native response. These findings should be taken into consideration when planning future clinical trials and may direct future preclinical research to optimize optogenetic approaches for visual restoration. The identified ERG signatures moreover may serve to track treatment efficiency in clinical trials.

neuroscience↗

bioRxiv2024

Enhanced restoration of visual code after targeting on bipolar cells compared to retinal ganglion cells with optogenetic therapy

Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like pre-clinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent. We address this deficit by comparing stimulus-response characteristics at single unit resolution in retina and dorsal lateral geniculate nucleus (dLGN) of retinally degenerate mice genetically engineered to express the opsin ReaChR in Grm6- or Brn3c-expressing cells (ON BC vs RGCs respectively). For both targeting strategies, we find ReaChR-evoked responses have equivalent sensitivity and can encode contrast across different background irradiances. Compared to ON BCs, targeting RGCs decreased response reproducibility and resulted in more stereotyped responses with reduced diversity in response polarity, contrast sensitivity and temporal frequency tuning. Recording ReaChR-driven responses in visually intact retinas confirmed that RGC-targeted ReaChR expression disrupts visual feature selectivity of individual RGCs. Our data show that while both approaches restore visual responses with impressive fidelity, ON BC targeting produces a richer visual code better approaching that of wildtype mice.

neuroscience↗

bioRxiv2024

Reconfiguration of the visual code and retinal cell type complement in closely related diurnal and nocturnal mice

How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours. Rhabdomys pumilio are diurnal and have substantially thicker inner retina and larger visual thalamus than nocturnal Mus musculus. High-density electrophysiological recordings of visual response features in the dorsal lateral geniculate nucleus (dLGN) reveals that Rhabdomys attains higher spatiotemporal acuity both by denser coverage of the visual scene and a selective expansion of elements of the code characterised by non-linear spatiotemporal summation. Comparative analysis of single cell transcriptomic cell atlases reveals that realignment of the visual code is associated with increased relative abundance of bipolar and ganglion cell types supporting OFF and ON-OFF responses. These findings demonstrate how changes in retinal cell complement can reconfigure the coding of visual information to match changes in visual needs.

neuroscience↗

bioRxiv2022

Functional integrity of visual coding following advanced photoreceptor degeneration

Photoreceptor degeneration sufficient to produce severe visual loss often spares the inner retina. This raises the hope that treatments using optogenetics or electrical stimulation, which generate a replacement light input signal in surviving neurons, may restore vision. The success of these approaches is dependent on the capacity of surviving circuits in the early stages of the visual system to generate and propagate an appropriate visual code in the face of neuroanatomical remodelling. To determine the capacity of surviving circuits in advanced retinal degeneration to present an appropriate visual code, we generated a transgenic mouse expressing the optogenetic actuator ReaChR in ON bipolar cells (second order neurons in the visual projection). After crossing this with the rd1 model of photoreceptor degeneration, we compared ReaChR derived responses with photoreceptor-driven responses in wildtype (WT) mice in retinal ganglion cells and visual thalamus. The ReaChR-driven responses in rd1 animals showed low photosensitivity, but in other respects generated a visual code that was very similar to WT. Furthermore, ReaChR rd1 units in the retina had high response reproducibility and showed sensitivity normalisation to code contrast stably across different background intensities. At the single unit level, ReaChR-derived responses exhibited broadly similar variation in light response polarity, contrast sensitivity and temporal frequency tuning as WT. Units from WT and ReaChR rd1 mice clustered together when subjected to unsupervised community detection based on stimulus-response properties. Our data reveal an impressive ability for surviving circuitry to recreate a rich visual code following advanced retinal degeneration and are promising for regenerative medicine in the central nervous system.

neuroscience↗

bioRxiv2020

Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons

There is no consensus on the best optogenetic tool for neuronal inhibition. Lamprey parapinopsin ( Lamplight) is a Gi/o-coupled bistable animal opsin that can be activated and deactivated by short and long wavelength light, respectively. Since native mechanisms of neuronal inhibition frequently employ Gi/o signalling, we asked here whether Lamplight could be used for optogenetic silencing. We show that short (405nm) and long (525nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, and that combining these wavelengths can be used to achieve intermediate levels of activity. We demonstrate that these properties can be applied to produce switchable and scalable neuronal hyperpolarisation, and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. We show that expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, and that 405 and 525nm stimuli can produce responses of opposite sign in output neurons of the retina. Lamplight-driven responses to both activating (405nm) and deactivating (525nm) light can occur within 500ms and be elicited by intensities at least 10x below threshold for available inhibitory optogenetic tools. We conclude that Lamplight can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and rapidly reversible.

neuroscience↗

bioRxiv2020

Neuraminidase activity mediates IL-6 production through TLR4 and p38/ERK MAPK signaling in MRL/lpr mesangial cells

Mesangial cells (MCs), considered the immune cell of the kidney, secrete a number of cytokines including IL-6, which serves as an autocrine factor for MCs stimulating proliferation. IL-6 is associated with disease in patients and mouse strains with lupus nephritis, promoting tissue damage. Previously, we demonstrated the activity or levels of the enzyme neuraminidase (NEU) is increased in the kidneys of lupus mice and urine of human patients with nephritis and that NEU activity plays a role in mediating IL-6 secretion from lupus prone MRL/lpr primary mouse MCs. In this study, we further elucidate the mechanisms by which NEU activity mediates cytokine production by primary lupus prone MCs. MRL/lpr primary MCs were cultured with lupus serum to stimulate cytokine production in the absence or presence of NEU activity inhibitor. Our results show lupus serum increases NEU activity, and secretion of GM-CSF and MIP1, in addition to IL-6, is significantly reduced when NEU activity is inhibited. mRNA expression of Il-6 and Gm-csf was also increased in response to lupus serum, and reduced when NEU activity was inhibited. Using neutralizing antibodies to specific receptors, inhibitors of MAP kinase signaling pathways, and LPS stimulation we show TLR4 and p38/ERK MAPK play a role in NEU-mediated secretion of IL-6. Together, our results suggest NEU activity plays an important role in the response of lupus prone MCs to factor(s) in lupus serum that stimulates IL-6 expression and secretion through TLR4-p38/ERK MAPK signaling, likely through desialyation of one or more glycoproteins in this pathway.

cell biology↗

bioRxiv2019

Extraocular, rod-like photoreceptors in a flatworm express xenopsin photopigment

Animals detect light using opsin photopigments. One recently classified opsin clade, the xenopsins, found in lophotrochozoans, challenges our views on opsin and photoreceptor evolution. Originally thought to belong to the Gi-coupled ciliary opsins, xenopsins are now understood to have diverged from ciliary opsins in pre-bilaterian times, but little is known about the cells that deploy these proteins, or if they form a photopigment and drive phototransduction. We characterized xenopsin in a flatworm, Maritigrella crozieri, and found that it is expressed in a larval eyespot, and in an abundant extraocular cell type around the adult brain. These distinct cells house hundreds of cilia in an intra-cellular vacuole (a phaosome). Cellular assays show Mc xenopsin forms a photopigment and couples to Gi/o in response to light. These findings reveal a novel photoreceptor cell type and opsin/G-protein couple, and highlight the convergent enclosure of photosensitive cilia in flatworm phaosomes and jawed vertebrate rods.

zoology↗

bioRxiv2019

Measuring vision using innate behaviours in mice with intact and impairedretina function

Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that dont require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.

neuroscience↗