Biology subjects

Ranson, A.

Publications and source records attributed to Ranson, A..

11 recordsLinked to original sources

bioRxiv2026

The chemorepellent effect of metformin limits bacterial penetration into mammalian mucus by altering bacterial motility

Metformin improves metabolic health and remodels the intestinal microbiota, yet how these microbial changes contribute to therapeutic benefits remains incompletely understood. We combined human metagenomics, quantitative analyses of bacterial behavior and ex vivo mucus models to investigate how metformin modulates host-microbiota interactions. Human metagenomics revealed metformin-associated enrichment of chemotaxis- and motility-related genes. At millimolar concentrations, metformin acted as a bacterial chemorepellent, an effect abolished by deletion of the chemotaxis regulator CheY and dependent on the chemoreceptor Tsr. Direct metformin exposure or fecal water from metformin-treated individuals reduced bacterial penetration into mucin, an effect reproduced in intestinal mucus from pigs fed a moderate-fat diet. Metformin treatment was further associated with reduced fecal flagellin activity and increased anti-flagellin IgA. Together, these findings identify bacterial chemotaxis as a target of metformin and reveal a mechanism by which metformin may limit bacterial access to the intestinal mucus barrier.

microbiology↗

bioRxiv2025

Feedforward and feedback population dynamics during binocular conflict in mouse visual cortex

Binocular rivalry arises when incongruent images are presented to the two eyes, producing stochastic alternations in perceptual dominance. While rivalry has been extensively studied in species with highly developed binocular vision, it is unclear whether similar representational dynamics occur in the mouse, a model system that allows large-scale cellular and circuit-level measurements. Here we used two-photon calcium imaging in awake mice to examine the population dynamics of primary visual cortex (V1) and long-range feedback axons from retrosplenial cortex (RSC) during presentation of dichoptically incongruent drifting gratings and natural movies. At the single-cell level, incongruent stimulation increased trial-to-trial variability of visually evoked responses relative to monocular stimulation. Linear SVM decoders trained on monocular responses revealed that during prolonged incongruent stimulation, V1 population activity alternated stochastically between representations of the two competing stimuli in a contrast-dependent manner. Decoder confidence was independent of pupil-indexed arousal state suggesting the dynamics observed may depend mostly on feedforward mechanisms. Transition analyses showed that switches in decoder output were typically driven by the emergence of responses to the ipsilateral stimulus, consistent with release from suppression of the non-dominant population. During incongruent presentation of natural movies, similar representational alternations were observed, indicating that rivalry-like dynamics were not dependent on orientation-selective adaptation. Imaging of RSC[->]V1 feedback axons revealed retinotopically specific, eye and orientation-selective signals that also alternated in dominance across time. These results establish the mouse as a model of rivalry-like cortical dynamics, demonstrate that both feedforward and feedback circuits contribute to representational alternation during binocular conflict, and provide a framework for mechanistic dissection of bistable perception.

neuroscience↗

bioRxiv2025

The functional organization of retrosplenial feedback to V1

Cortical feedback from higher frontal and association areas to early sensory cortex is thought to contribute to a range of cognitive processes in which sensory signals are processed in a context sensitive manner. Despite the ubiquity of feedback circuitry in the cortex, the information carried by feedback connections, and the principles governing how it is targeted from area to area remains poorly understood. Here we characterized the functional properties of a prominent feedback circuit which links retrosplenial cortex (RSC) and primary visual cortex (V1). We found that RSC[->]V1 axons relay retinotopically selective signals to V1 which at a coarse scale match the region of the V1 retinotopic map innervated, were tuned for spatial and temporal frequency, but not tuned for orientation. Two-color imaging of RSC[->]V1 boutons and local L2/3 V1 neurons further revealed that at a finer scale RSC[->]V1 bouton receptive fields are systematically offset relative to those of V1 in the nasal direction, consistent with RSC[->]V1 boutons conveying signals predictive of upcoming V1 activity in the retinotopic region innervated during forward movement.

neuroscience↗

bioRxiv2025

Disruption of IgA-mediated aggregation at weaning favors mucus encroachment by commensal bacteria

Disruption of the gut mucus barrier is a critical step in the development of infec-tious or chronic inflammatory diseases. However, there are no clear links between developmental stages, diet, and the mechanical and biochemical properties of mucus. The transition from suckling to weaning is a pivotal stage in the devel-opment of the mucus barrier in mammals, with significant implications for the health and morbidity of mammalian infants. Here, using a novel microfluidic device, we investigate the penetration and organizational properties of motile Escherichia coli bacteria at the mucus interface using purified intestinal mucus collected from cohorts of piglets before and after weaning. In weaned piglets, E. coli penetrate more than 100 {micro}m into the mucus, a distance greater than the physiological thickness of the mucus layer in vivo. In contrast, for suckling piglets significant bacterial aggregation is observed at the interface, hindering the pene-tration process. Using the supernatant obtained from purified mucus of suckling piglets, we were able to restore bacterial aggregation in weaned piglet mucus and limit penetration. Interestingly, we also achieved the same result using purified human breast milk immunoglobulin A (IgA), which is known to promote bacterial aggregation. Our results emphasize the importance of mucosal immunoglobulin A (IgA) specificity in relation to the mothers immunological history, which is primarily transmitted through breast milk and lost during weaning. This also might explain why the suckling/weaning transition is, among other issues, a crit-ical window associated with a high incidence of gastrointestinal infections, before autologous IgA-mediated definite protection is acquired. Studying bacterial pen-etration in complex fluids using this new in vitro microfluidic device will pave the way for future research and the development of predictive tools for use in medical research trials.

microbiology↗

bioRxiv2023

Experience dependent plasticity of higher visual cortical areas in the mouse

Introduction ABSTRACT Introduction Materials and Methods Results Discussion CRediT authorship contribution... Funding References Since the pioneering work by Hubel and Wiesel on cats and monkeys in the 1960s and 1970s (Wiesel and Hubel, 1963; Hubel et al., 1977) ocular dominance (OD) plasticity has become one of the classic paradigms for the study of experience-dependent brain plasticity. Occluding one eye by monocular deprivation (MD) shifts responses of visual cortical neurons towards the open eye, in particular during a critical period early in life Hubel Wiesel (Hubel and Wiesel, 1970; Olson and Freeman, 1978). It also results in a substantial loss of visual acuity in the deprived eye ( ...

neuroscience↗

bioRxiv2021

Endogenous recruitment of frontal-sensory circuits during visual discrimination

A long-range circuit linking anterior cingulate cortex (ACC) to primary visual cortex (V1) has been previously proposed to mediate visual selective attention in mice during visually guided behaviour. Here we used in vivo two-photon functional imaging to measure endogenous activity of ACC neurons projecting to layer 1 of V1 (ACC-V1axons) in mice either passively viewing stimuli or performing a go/no-go visually guided task. We observed that while ACC-V1axons were recruited under these conditions, this was not linked to enhancement of neural or behavioural measures of sensory coding. Instead, ACC-V1axon activity was observed to be associated with licking behaviour, modulated by reward, and biased towards task relevant sensory cortex.

neuroscience↗

bioRxiv2021

Abi3 regulates microglial ramification and dynamic tissue surveillance in vivo.

A rare coding variant of Abelson-interactor gene family member 3 (Abi3) is associated with increased risk of late-onset Alzheimers Disease (AD). Although Abi3 is recognised as a core microglial gene, its role in microglia is largely unknown. Here we demonstrate that Abi3 is crucial for normal microglial morphology, distribution, and homeostatic tissue surveillance activity in vivo.

neuroscience↗

bioRxiv2020

RPG: A low-cost, open-source, high-performance solution for displaying visual stimuli

The development of new high throughput approaches for neuroscience such as high-density silicon probes and 2-photon imaging have led to a renaissance in visual neuroscience. However, generating the stimuli needed to evoke activity in the visual system still represents a non-negligible difficulty for experimentalists. While several widely used software toolkits exist to deliver such stimuli, they all suffer from some shortcomings. Primarily, the hardware needed to effectively display such stimuli comes at a significant financial cost, and secondly, triggering and/or timing the stimuli such that it can be accurately synchronized with other devices requires the use of legacy hardware, further hardware, or bespoke solutions. Here we present RPG, a Python package written for the Raspberry Pi, which overcomes these issues. Specifically, the Raspberry Pi is a low-cost, credit card sized computer with general purpose input/output pins, allowing RPG to be triggered to deliver stimuli and to provide real-time feedback on stimulus timing. RPG delivers stimuli at >60 frames per second and the feedback of frame timings is accurate to 10s of microseconds. We provide a simple to use Python interface that is capable of generating drifting sine wave gratings, Gabor patches and displaying raw images/video.

neuroscience↗

bioRxiv2019

Stable encoding of visual cues in the mouse retrosplenial cortex

The rodent retrosplenial cortex functions as an integrative hub for sensory and motor signals, serving roles in both navigation and memory. While retrosplenial cortex (RSC) is reciprocally connected with the sensory cortex, the form in which sensory information is represented in the retrosplenial cortex and how it interacts with behavioural state is unclear. Here, we used 2-photon cellular imaging of neural activity of putative excitatory (CaMKII expressing) and inhibitory (parvalbumin expressing) neurons to measure visual and running evoked activity in RSC and compare it to primary visual cortex (V1). We found that stimulus position and orientation information was preserved between V1 and RSC, and additionally that positional information was organised topographically. Stimulus directional preference was biased towards nasal-temporal flow. Locomotion modulation of activity of single neurons, both in darkness and light, was also more pronounced in RSC than V1, and strongest in parvalbumin-positive neurons. Longitudinal measurements of single neurons showed that these response features were stably maintained over many weeks. These data provide evidence for stable representations of visual cues in retrosplenial cortex which are highly spatially selective. These may provide sensory data to contribute to the formation of memories of spatial information.

neuroscience↗

bioRxiv2017

NMDAR hypofunction increases top-down influence on sensory processing

Converging evidence implicates NMDAR disruption in the pathogenesis of schizophrenia, a condition in which perceptual disturbances are prominent. To explore how NMDAR hypofunction causes perceptual symptoms we investigated activity in cortical sensory circuits in awake behaving mice during pharmacologically induced NMDAR hypofunction. We observed a reduction in sensory-driven activity in V1 while input from the anterior cingulate cortex simultaneously increased, suggesting NMDAR hypofunction may lead to altered perception by modifying the balance of top-down and bottom-up processing.

neuroscience↗

bioRxiv2016

Stability and plasticity of contextual modulation in the mouse visual cortex

Activity of neurons in primary sensory cortex is shaped by visual and behavioural context. However the long-term stability of the influence of contextual factors in the mature cortex remains poorly understood. To investigate this we used 2-photon calcium imaging to track the influence of surround suppression and locomotion on individual neurons over 14 days. We found that highly active excitatory neurons and PV+ interneurons exhibited relatively stable modulation by visual context. Similarly most neurons exhibited a stable yet distinct degree modulation by locomotion. In contrast less active excitatory neurons exhibited plasticity in visual context influence resulting in increased suppression. These findings suggest that the mature visual cortex possesses stable subnetworks of neurons, differentiated by cell-type and activity level, which have distinctive and stable interactions with sensory and behavioural context, as well as other less active and more labile neurons which are sensitive to visual experience.

neuroscience↗