Biology subjects

Ligneul, C.

Publications and source records attributed to Ligneul, C..

7 recordsLinked to original sources

bioRxiv2026

High-throughput light-sheet 3D microscopy of whole rodent brain microstructure for integration with MRI

Whole-brain cellular mapping is essential for understanding how differences in cellular architecture shape brain organisation and function. Magnetic Resonance Imaging (MRI) provides whole-brain coverage in humans and animal models but is only indirectly sensitive to cellular features. Integrating MRI with whole-brain microscopy is therefore critical for interpreting existing microstructural MRI metrics and developing new, more specific ones. Here, we present a scalable cross-resolution framework that integrates 3D light-sheet microscopy (LSM) of intact rodent brains with diffusion MRI (dMRI) to bridge cellular and macroscopic brain imaging. By combining active electrotransport-based tissue clearing and immunolabelling with accelerated LSM acquisitions, we achieve whole-brain multiplexed mapping of neuronal and glial populations in intact rodent brains on timescales comparable to conventional histology and 2D microscopy. This throughput enables LSM and MRI integration at scale, linking macroscopic MRI contrasts to microscopic cellular features within the same tissue. We apply this framework across eight genetically diverse mouse strains to develop predictive models of 3D microscopy-derived cellular features from multi-shell dMRI-derived contrasts. We demonstrate that data-driven combinations of state-of-the-art dMRI contrasts predict neuronal and astrocytic features better than individual contrasts, across all animals. Our novel approach enables 3D microscopy to guide the development and interpretation of microstructural MRI measures that are ultimately translatable to the living human brain.

neuroscience↗

bioRxiv2026

Longitudinal neurochemical profiling after experimental stroke using edited MR spectroscopy

Background: Alterations in excitatory and inhibitory neurotransmission contribute to stroke pathology and recovery, yet longitudinal assessment of these changes in vivo remains limited. We investigated the feasibility of longitudinal edited proton magnetic resonance spectroscopy (1H-MRS) to quantify {gamma}-aminobutyric acid (GABA) and glutamate following experimental focal cerebral ischaemia. Methods: Male rats underwent endothelin-1-induced striatal ischaemia or sham surgery. Longitudinal edited 1H-MRS was performed at baseline and 2-, 7- and 30-days post-stroke at 7-tesla with a MEGA-sLASER sequence. A voxel was positioned within the ipsilesional motor cortex adjacent to the lesion. Behavioural outcomes (grip strength, adhesive removal and CatWalk gait analysis) were assessed alongside spectroscopy, and immunohistochemistry for Iba1, GFAP and ICAM-1 was performed at 30 days. Results: Stroke induced a transient reduction in GABA+/tCr within the ipsilesional motor cortex, with significantly lower concentrations than sham animals at 7 days (p<0.05), returning to baseline by 30 days. Glutamate/tCr and GABA/glutamate ratio were unchanged throughout the study. Behavioural deficits were mild, with significant effects on motor outcomes such as grip strength, gait swing speed and paw placement, while sensory areas of the brain seemed largely unaffected. Histological analysis revealed no persistent differences in cortical Iba1, GFAP or ICAM-1 immunoreactivity at 30 days. Conclusions: Longitudinal 1H-MRS is a feasible approach for monitoring dynamic changes in inhibitory neurochemistry following experimental stroke. The transient reduction in peri-lesional GABA, despite minimal behavioural impairment and an absence of persistent cortical inflammation, supports the use of edited spectroscopy as a translational tool to investigate neurochemical mechanisms underlying network dynamics in post-stroke recovery.

neuroscience↗

bioRxiv2025

Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction

Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited neurodegenerative disorders with no effective treatment. Aberrant signalling through the metabotropic glutamate receptor (mGluR1) has been implicated in several SCAs. However, whether disease is caused through decreased or increased mGluR1 signalling remains controversial. Here, we generate the first mouse model of enhanced mGluR1 function by introducing a gain-of-function mutation (p.Y792C) that causes SCA44 in the metabotropic glutamate receptor 1 (Grm1) gene. Grm1 mutant mice recapitulate key pathophysiological aspects of SCA, including progressive motor deficits, altered climbing fibre innervation and perturbed Purkinje cell spontaneous activity. We report that changes in synaptic innervation and intrinsic Purkinje cell activity upon overactive mGluR1 signalling manifest in a lobule- and disease-stage-specific manner. Our findings demonstrate that enhanced mGluR1 function is a direct and specific driver of Purkinje cell dysfunction and pathology and provide a mechanism for understanding the selective vulnerability of different Purkinje cell populations in SCA.

neuroscience↗

bioRxiv2025

Perinatal environmental enrichment affects murine neonates' brain structure before their active engagement with environment

Early life experiences shape individuals. Environmental enrichment, an experimental paradigm used to study the effect of increased environmental complexity and novelty in animal models, has long been recognised for its broad effect on nervous system function and behaviour. In adult rodents, structural changes in the brain due to enriched environments are well documented, notably in the hippocampus. However, the effect of environmental enrichment on the developing brain during early life is not well understood. This study aims to investigate how environmental enrichment affects brain development during the critical perinatal period, and how such effects compare to those observed during adulthood. We use high-resolution MRI to measure the brain structure of mouse neonates at postnatal day 7, born either in an enriched or a standard environment. We show that rodents exhibit brain structure differences as early as postnatal day 7. However, the regional changes observed differ from those in adulthood: hippocampal changes are limited, but changes in the hindbrain, the dorsal striatum, and the medial habenula are strong. Given the lack of direct interaction between neonates and the environment at P7, we hypothesised that maternal care may mediate these effects. We show that maternal care differs between enriched and standard environments, that maternal care correlates with brain structure changes in the neonates, and that maternal care and enriched environment affect brain structure similarly. This suggests that early changes in brain structure due to environmental enrichment are at least partly mediated by maternal care. This study provides novel insight into the differential effect of enriched environment on early brain development in rodents.

neuroscience↗

bioRxiv2023

Diffusion MRS tracks distinct trajectories of neuronal development in the cerebellum and thalamus of rat neonates.

It is currently impossible to non-invasively assess cerebellar cell structure during early development. Here we propose a novel approach to non-invasively and longitudinally track cell-specific development using diffusion-weighted magnetic resonance spectroscopy in combination with microstructural modelling. Tracking metabolite diffusion allows us to probe cell-specific developmental trajectories in the cerebellum and thalamus of healthy rat neonates from post-natal day (P) 5 to P30. Additionally, by comparing different analytical and biophysical microstructural models we can follow the differential contribution of cell bodies and neurites during development. The thalamus serves as a control region to assess the sensitivity of our method to microstructural differences between the regions. We found significant differences between cerebellar and thalamic metabolites diffusion properties. For most metabolites, the signal attenuation is stronger in the thalamus, suggesting less restricted diffusion compared to the cerebellum. There is also a trend for lower signal attenuation and lower ADCs with increasing age, suggesting increasing restriction of metabolite diffusion. This is particularly striking for taurine in the thalamus. We use biophysical modelling to interpret these differences. We report a decreased sphere fraction (or an increased neurite fraction) with age for taurine and total creatine in the cerebellum, marking dendritic growth. Surprisingly, we also report a U-shape trend for segment length (the distance between two embranchments in a dendritic tree) in the cerebellum agreeing with age-matching morphometry of openly available 3D-Purkinje reconstructions. Results demonstrate that diffusion-weighted MRS probes early cerebellar neuronal development non-invasively.

neuroscience↗

bioRxiv2023

Universal Dynamic Fitting of Magnetic Resonance Spectroscopy

Dynamic (2D) magnetic resonance spectroscopy is a collection of techniques where acquisitions of spectra are repeated under varying experimental or physiological conditions. Dynamic MRS comprises a rich set of contrasts, including diffusion-weighted, relaxation-weighted, functional, edited, or hyperpolarized spectroscopy, leading to quantitative insights into multiple physiological or microstructural processes. Conventional approaches to dynamic MRS analysis ignore the shared information between spectra, and instead proceed by independently fitting noisy individual spectra before modelling temporal changes in the parameters. Here we propose a universal dynamic MRS toolbox which allows simultaneous fitting of dynamic spectra of arbitrary type. A simple interface allows information to be shared and precisely modelled across spectra to make inferences on both spectral and dynamic processes. We demonstrate and thoroughly evaluate our approach in three types of dynamic MRS techniques. Simulations of functional and edited MRS are used to demonstrate the advantages of dynamic fitting. Analysis of synthetic functional 1H-MRS data shows a marked decrease in parameter uncertainty as predicted by prior work. Analysis with our tool replicates the results of two previously published studies using the original in vivo functional and diffusion-weighted data. Finally, joint spectral fitting with diffusion orientation models is demonstrated in synthetic data. The toolbox is shared as a fully open-source software with comprehensive documentation, example data, and tutorials.

neuroscience↗

bioRxiv2018

Diffusion-weighted magnetic resonance spectroscopy enables cell-specific monitoring of astrocyte reactivity in vivo

The diffusion of brain intracellular metabolites, as measured using diffusion-weighted magnetic resonance spectroscopy in vivo, is thought to specifically depend on the cellular structure constraining them. However, it has never been established that variations of metabolite diffusion, e.g. as observed in some diseases, could indeed be linked to alterations of cellular morphology. Here we demonstrate, in a mouse model of reactive astrocytes, that advanced diffusion-weighted magnetic resonance spectroscopy acquisition and modeling techniques enable non-invasive detection of reactive astrocyte hypertrophy (increased soma radius, increased fiber radius and length), as inferred from variations of myo-inositol diffusion, and as confirmed by confocal microscopy ex vivo. This establishes that specific alterations of intracellular metabolite diffusion can be measured and related to cell-specific morphological alterations. Furthermore, as reactive astrocytes are a hallmark of many brain pathologies, this work opens exciting perspectives for neuroscience and clinical research.

bioinformatics↗