Biology subjects

Merlin, S.

Publications and source records attributed to Merlin, S..

8 recordsLinked to original sources

bioRxiv2026

A comprehensive genetic study of the vaginal microbiota composition of Holstein cows

The vaginal microbiota is a potentially important component of the bovine reproductive tract and has been associated with fertility, health, and production-related traits in cattle. However, the impact of host genetics on the bovine vaginal microbiota and its genetic correlations with animal performance remain largely unexplored. To investigate this, we performed a comprehensive genetic study of the vaginal microbiota in Holstein cows. Vaginal swabs from 681 lactating cows across 18 herds in Northern France were collected, along with records of fertility, milk production, and health traits. The microbiota samples were sequenced for the 16S rRNA gene, generating count tables of amplicon sequence variants (ASV). We estimated genetic parameters for vaginal microbiota -diversity (Chao1, Shannon, and Simpson indices) and {beta}-diversity (Bray-Curtis dissimilarity matrix), as well as the centered log-ratio (CLR)-transformed abundances of taxa present in more than 50% of samples. Across the 173 analyzed taxa, heritability estimates ranged from low to moderate (h2 = 0.09 to 0.38) for five genera, three families, eight orders, three classes, and one phylum. Notably, the order Flavobacteriales exhibited the highest heritability estimate. The study also highlighted genetic correlations between heritable microbiota traits and host phenotypes related to fertility, production, and health. Sequence-based genome-wide association studies (GWAS) identified biologically relevant signals, including a quantitative trait locus (QTL) for the genus Alloprevotella on chromosome 6, with lead variants located within the NAF1 gene. Additionally, two signals on chromosome 17 for the Bacteroidales order and the Bacteroida class co-localized with IL15. Our findings show that host genetics contributes to variation in specific components of the bovine vaginal microbiota and suggest that microbiome-related traits may warrant further investigation as potential indicators in dairy cattle breeding and management research.

genetics↗

bioRxiv2024

Primate V2 Receptive Fields Derived from Anatomically Identified Large-Scale V1 Inputs

In the primate visual system, visual object recognition involves a series of cortical areas arranged hierarchically along the ventral visual pathway. As information flows through this hierarchy, neurons become progressively tuned to more complex image features. The circuit mechanisms and computations underlying the increasing complexity of these receptive fields (RFs) remain unidentified. To understand how this complexity emerges in the secondary visual area (V2), we investigated the functional organization of inputs from the primary visual cortex (V1) to V2 by combining retrograde anatomical tracing of these inputs with functional imaging of feature maps in macaque monkey V1 and V2. We found that V1 neurons sending inputs to single V2 orientation columns have a broad range of preferred orientations, but are strongly biased towards the orientation represented at the injected V2 site. For each V2 site, we then constructed a feedforward model based on the linear combination of its anatomically-identified large-scale V1 inputs, and studied the response proprieties of the generated V2 RFs. We found that V2 RFs derived from the linear feedforward model were either elongated versions of V1 filters or had spatially complex structures. These modeled RFs predicted V2 neuron responses to oriented grating stimuli with high accuracy. Remarkably, this simple model also explained the greater selectivity to naturalistic textures of V2 cells compared to their V1 input cells. Our results demonstrate that simple linear combinations of feedforward inputs can account for the orientation selectivity and texture sensitivity of V2 RFs.

neuroscience↗

bioRxiv2023

Characterization of bovine vaginal microbiota and its relationship with host fertility, health, and production

BackgroundBecause of its potential influence on the hosts phenotype, increasing attention is paid to organ-specific microbiota in several animal species, including cattle. However, ecosystems other than those related to the digestive tract remain largely understudied. In particular, little is known about the vaginal microbiota of ruminants despite the importance of the reproductive functions of cows in a livestock context, where fertility disorders represent one of the primary reasons for culling. ResultsIn the present study, we aimed at better characterizing the vaginal microbiota of dairy cows through 16S rRNA sequencing, using a large cohort of Holstein cows from Northern France. Our results allowed to define a core microbiota of the dairy cows vagina, and highlighted that 90% of the sequences belonged to the Firmicutes, the Proteobacteria, and the Bacteroidetes phyla. The core microbiota was composed of four phyla, 16 families, 14 genera and only one amplicon sequence variant (ASV), supporting the idea of the high diversity of vaginal microbiota within the studied population. This variability was partly explained by various environmental factors such as the herd, the sampling season, the lactation rank and the lactation stage. In addition, we investigated potential associations between the diversity and the composition of the vaginal microbiota and several health-, performance-, and fertility-related phenotypes. Our analyses highlighted significant associations between the and {beta}- diversities and several traits including the first insemination outcome, the productive longevity, and the culling. Besides, relevant phenotypes were correlated with the abundance of several genera, some of which, such as Leptotrichia, Streptobacillus, Methylobacterium-Methylorubrum, or Negativibacillus, were linked to multiple traits. ConclusionConsidering the large number of samples, which were collected in commercial farms, and the diversity of the phenotypes considered, this study represents a first step towards a better understanding of the close relationship between the vaginal and the dairy cows phenotypes.

microbiology↗

bioRxiv2023

FVIII interacts with cell surface to regulate endothelial cell functionality

Haemophilia A (HA) is a rare bleeding disorder caused by factor 8 (F8) mutations. Clinical manifestations are spontaneous bleedings that primarily consist of hemarthrosis and intracranial haemorrhages. To date, the impairment of vessel stability in HA patients and the correlation between FVIII and endothelial functionality is poorly understood. Here we show that FVIII plays a role in endothelial cell functionality. Blood Outgrowth endothelial cells (BOECs) knockout generated by CRISPR/Cas9, HA BOECs and HA iPSCs-derived ECs showed alteration of vessel-formation, endothelial cell migration, and vessel permeability. Importantly, the impaired EC phenotype was rescued by treatment with recombinant human FVIII or by lentiviral vector (LV) expressing FVIII. The FVIII function on endothelium was confirmed in vivo in a mouse model of severe HA which showed that an altered angiogenesis and vesselpermeability could be treated by exogenous FVIII. BOECstranscriptomic profiles revealed that FVIIIregulates the expression of endothelial basement membrane and extracellular matrix genes. Furthermore, exogenous expression of Nidogen2, identified as a FVIII regulated gene, restored the extracellular matrix integrity and EC functionality of HA ECs. In conclusion, FVIII is not only a coagulation factor but also an endothelial cell autocrine factor which promotes vessel stability.

molecular biology↗

bioRxiv2023

Immp2l knockdown increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a mouse model of Tourette syndrome and autism spectrum disorder

Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms of autism spectrum disorder (ASD) and Gilles de la Tourette syndrome (GTS), such as tics and repetitive behaviours, may emerge because of imbalances in these neurocircuits. We have recently developed a model of ASD and GTS by knocking down Immp2l, a mitochondrial gene frequently associated with these disorders. The current study sought to determine whether Immp2l knockdown (KD) in male mice alters flexible, goal- or cue-driven behaviour using procedures specifically designed to examine response-outcome and stimulus-response associations, which underlie goal-directed and habitual behaviour, respectively. Whether Immp2l KD alters neuron density in cortico-striatal neurocircuits known to regulate these behaviours was also examined. Immp2l KD mice and wild type-like mice (WT) were trained on Pavlovian and instrumental learning procedures where auditory cues predicted food delivery and lever-press responses earned a food outcome. It was demonstrated that goal-directed learning was not changed for Immp2l KD mice compared to WT mice, as lever-press responses were sensitive to changes in the value of the food outcome, and to contingency reversal and degradation. There was also no difference in the capacity of KD mice to form habitual behaviours compared to WT mice following extending training of the instrumental action. However, Immp2l KD mice were more responsive to auditory stimuli paired with food as indicated by a non-specific increase in lever response rates during Pavlovian-to-instrumental transfer. Finally, there were no alterations to neuron density in striatum or any prefrontal cortex or limbic brain structures examined. Thus, the current study suggests that Immp2l is not necessary for learned maladaptive goal or stimulus driven behaviours in ASD or GTS, but that it may contribute to increased capacity for external stimuli to drive behaviour. Alterations to stimulus-driven behaviour could potentially influence the expression of tics and repetitive behaviours, suggesting that genetic alterations to Immp2l may contribute to these core symptoms in ASD and GTS. Given that this is the first application of this battery of instrumental learning procedures to a mouse model of ASD or GTS, it is an important initial step in determining the contribution of known risk-genes to goal-directed versus habitual behaviours, which should be more broadly applied to other rodent models of ASD and GTS in the future.

neuroscience↗

bioRxiv2020

Stream-Specific Feedback Inputs to the Primate Primary Visual Cortex

The sensory neocortex consists of hierarchically-organized areas reciprocally connected via feedforward and feedback circuits. Feedforward connections shape the receptive field properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. Feedback connections, instead, have been implicated in top-down modulations, such as attention, prediction and sensory context. However, their computational role remains unknown, partly because we lack knowledge about rules of feedback connectivity to constrain models of feedback function. For example, it is unknown whether feedback connections maintain stream-specific segregation, or integrate information across parallel streams. Using selective viral-mediated labeling of feedback connections arising from specific cytochrome-oxidase stripes of macaque visual area V2, we find that feedback to the primary visual cortex (V1) is organized into parallel streams resembling the reciprocal feedforward pathways. These results suggest that functionally-specialized V2 feedback channels modulate V1 responses to specific stimulus attributes, an organizational principle that could extend to feedback pathways in other sensory systems.

neuroscience↗

bioRxiv2017

Distinct Laminar Processing of Local and Global Context in Primate Primary Visual Cortex

Visual perception is profoundly affected by spatial context. In visual cortex, neuronal responses to stimuli inside their receptive field (RF) are suppressed by contextual stimuli in the RF surround (surround suppression). How do neuronal RFs integrate information across visual space, and what role do different cortical layers play in the processing of spatial context? By recording simultaneously across all layers of macaque primary visual cortex, while presenting visual stimuli at increasing distances from the recorded cells RF, we find that near vs. far stimuli activate distinct layers. Stimuli in the near-surround evoke the earliest subthreshold responses in superficial and deep layers, and cause the earliest surround suppression of spiking responses in superficial layers. Instead, far-surround stimuli evoke the earliest subthreshold responses in feedback-recipient layers, i.e. 1 and the lower half of the deep layers, and suppress visually-evoked spiking responses almost simultaneously in all layers, except 4C, where suppression emerges latest. Our results reveal unique contributions of the cortical layers to the processing of local and global spatial context, and suggest distinct underlying circuits for local and global signal integration.

neuroscience↗

bioRxiv2016

CORTICO-CORTICAL FEEDBACK CONTROLS SPATIAL SUMMATION IN PRIMATE VISUAL CORTEX

In the cerebral cortex, sensory information travels along feedforward connections through a hierarchy of areas, which, in turn, send a denser network of feedback connections to lower-order areas. Feedback has been implicated in attention, expectation, and sensory context, but the cellular mechanisms underlying these diverse feedback functions are unknown. Using specific optogenetic inactivation of feedback connections in the primate visual cortex, we have identified the cellular mechanisms of feedback-mediated modulations of early sensory processing. Specifically, we found that feedback modulates receptive field size, surround suppression and response gain, similar to the modulatory effects of visual spatial attention. A recurrent network model captured these effects. These feedback-mediated modulations allow higher-order cortical areas to dynamically regulate spatial resolution, sensitivity to image features, and efficiency of coding natural images in lower-order cortical areas.

neuroscience↗