Biology subjects

Martineau, E.

Publications and source records attributed to Martineau, E..

7 recordsLinked to original sources

bioRxiv2026

Inhibitory Interneurons Modulate Neurovascular Coupling Primarily Through Indirect Circuit Mechanisms

Neurovascular coupling (NVC) links neuronal activity to local hemodynamics, underlies functional imaging signals such as fMRI, and is often disrupted in neurological disorders. Although inhibitory interneurons can directly signal to blood vessels, their relative contribution to NVC during sensory processing remains unclear. Here, we combined mesoscale cell-type-specific calcium imaging, hemodynamic imaging, and chemogenetic silencing to determine how parvalbumin-expressing (PV) and somatostatin-expressing (SOM) interneurons shape functional hyperemia in the mouse barrel cortex. During single-whisker stimulations, PV and SOM activity exhibited strong spatial co-variation with local hemodynamic responses across the barrel field. Silencing PV interneurons produced variable changes in local hemodynamic responses that closely tracked excitatory activity while disproportionately broadening the spatial spread of the hemodynamic response, whereas SOM silencing exerted comparatively modest effects. Together, these findings suggest that NVC predominantly reflects overall circuit activity, even when inhibitory signaling is broadly impaired.

neuroscience↗

bioRxiv2022

Store-Operated Ca2+ Channels Mediate Microdomain Ca2+ Signals and Amplify Gq-Coupled Ca2+ Elevations in Capillary Pericytes

Pericytes are multifunctional cells of the vasculature that are vital to brain homeostasis, yet many of their fundamental physiological properties remain unexplored. Ca2+ is a ubiquitous second messenger across cell-types, where it mediates diverse functions such as contractility and gene transcription. It is therefore important to understand the cellular mechanisms underlying Ca2+ signalling in capillary pericytes. Here, we performed pharmacological and ion substitution experiments to investigate the mechanisms underlying pericyte Ca2+ signaling in acute cortical brain slices of PDGFR{beta}-GCaMP6f mice. We report that in mid-capillary bed pericytes ([≥] 4th branch order), spontaneous microdomain Ca2+ signals are dependent on extracellular Ca2+, but largely independent of depolarization, L- and T-type voltage-gated calcium channels (VGCCs), and TRPC3/6 channels. In contrast, these microdomain signals were inhibited by multiple Orai channel blockers, including the specific antagonist GSK-7975A. Furthermore, capillary pericytes exhibited classical store operated calcium entry (SOCE) following store depletion that was sensitive to GSK-7975A and required for amplification of intracellular Ca2+ increases evoked by the vasoconstrictor endothelin-1. These results suggest that Orai SOCE mediates microdomain Ca2+ signals at rest and amplifies Gq-GPCR coupled Ca2+ elevations in capillary pericytes. Thus, SOCE is a major regulator of pericyte Ca2+ and a target for manipulating their function in health and disease.

neuroscience↗

bioRxiv2020

MiSiC, a general deep learning-based method for the high-throughput cell segmentation of complex bacterial communities

Studies of microbial communities by live imaging require new tools for the robust identification of bacterial cells in dense and often inter-species populations, sometimes over very large scales. Here, we developed MiSiC, a general deep-learning-based segmentation method that automatically segments a wide range of spatially structured bacterial communities with very little parameter adjustment, independent of the imaging modality. Using a bacterial predator-prey interaction model, we demonstrate that MiSiC enables the analysis of interspecies interactions, resolving processes at subcellular scales and discriminating between species in millimeter size datasets. The simple implementation of MiSiC and the relatively low need in computing power make its use broadly accessible to fields interested in bacterial interactions and cell biology.

microbiology↗

bioRxiv2020

Properties of Glial Cell at the Neuromuscular Junction are Incompatible with synaptic repair in the SOD1G37R ALS mouse model

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motoneurons in a motor-unit (MU) dependent manner. Glial dysfunction contributes to numerous aspects of the disease. At the neuromuscular junction (NMJ), early alterations in perisynaptic Schwann cell (PSC), glial cells at this synapse, may impact their ability to regulate NMJ stability and repair. Indeed, muscarinic receptors (mAChR) regulate the repair phenotype of PSCs and are overactivated at disease-resistant NMJs (Soleus muscle) in SOD1G37R mice. However, it remains unknown whether this is the case at disease-vulnerable NMJs and whether it translates into an impairment of PSC-dependent repair mechanisms. We used Soleus and Sternomastoid muscles from SOD1G37R mice and performed Ca2+-imaging to monitor PSC activity and used immunohistochemistry to analyze their repair and phagocytic properties. We show that PSC mAChR-dependent activity was transiently increased at disease-vulnerable NMJs (Sternomastoid muscle). Furthermore, PSCs from both muscles extended disorganized processes from denervated NMJs and failed to initiate or guide nerve terminal sprouts at disease-vulnerable NMJs, a phenomenon essential for compensatory reinnervation. This was accompanied by a failure of numerous PSCs to upregulate Galectin-3 (MAC-2), a marker of glial axonal debris phagocytosis, upon NMJ denervation in SOD1 mice. Finally, differences in these PSC-dependent NMJ repair mechanisms were MU-type dependent, thus reflecting MU vulnerability in ALS. Together, these results reveal that neuron-glia communication is ubiquitously altered at the NMJ in ALS. This appears to prevent PSCs from adopting a repair phenotype, resulting in a maladapted response to denervation at the NMJ in ALS. SIGNIFICANCE STATEMENTUnderstanding how the complex interplay between neurons and glial cells ultimately lead to the degeneration of motor neurons and loss of motor function is a fundamental question to comprehend amyotrophic lateral sclerosis. An early and persistent alteration of glial cell activity takes place at the neuromuscular junction (NMJ), the output of motor neurons, but its impact on NMJ repair remains unknown. Here, we reveal that glial cells at disease-vulnerable NMJs often fail to guide compensatory nerve terminal sprouts and to adopt a phagocytic phenotype on denervated NMJs in SOD1G37R mice. These results show that glial cells at the NMJ elaborate an inappropriate response to NMJ degeneration in a manner that reflects motor-unit vulnerability and potentially impairs compensatory reinnervation.

neuroscience↗

bioRxiv2020

Combining mass spectrometric platforms for lipidome investigation - Application to the characterisation of disruptions in the lipid profile of pig serum upon β agonist treatment

In the last decade, many mass spectrometric fingerprinting methods dedicated to lipidomics have been proposed: either non-targeted approaches, coupled with annotation methods, or targeted strategies, aiming at specifically monitoring a limited number of substances. In a general public health perspective and through a strategy combining non-targeted and targeted lipidomics MS-based approaches, this study aims at identifying disrupted patterns in serum lipidome upon growth promoter treatment in pig and evaluating the relative contributions of the three platforms involved. Pig serum samples collected during an animal experiment involving control and treated animals, whose food had been supplemented with ractopamine, were extracted and characterised using three MS strategies: Non-targeted RP LC-HRMS; the targeted Lipidyzer platform (differential ion mobility associated with shotgun lipidomics) and a homemade LC-HRMS triglyceride platform. The three different platforms showed complementarity insight into lipid characterisation, which, applied to a selected set of samples, enabled highlighting specific lipid profile patterns involving various lipid classes, mainly in relation with cholesterol esters, sphingomyelins, lactosylceramide, phosphatidylcholines and triglycerides. Thanks to the combination of both non-targeted and targeted MS approaches, the exploration of various compartments of the pig serum lipidome could be performed, including commonly characterised lipids (Lipidyzer), triglyceride isomers (Triglyceride platform) -whose accurate analysis was considered an analytical challenge, and unique lipid features (non-targeted LC-HRMS). Thanks to their respective characteristics, the complementarity of the three tools could be demonstrated for public health purposes, with enhanced lipidome coverage, level of characterisation and applicability.

biochemistry↗

bioRxiv2017

The nucleoid as a scaffold for the assembly of bacterial signaling complexes

The FrzCD chemoreceptor from the gliding bacterium Myxococcus xanthus forms cytoplasmic clusters that occupy a large central region of the cell body also occupied by the nucleoid. In this work, we show that FrzCD directly binds to the nucleoid with its N-terminal positively charged tail and recruits active signaling complexes at this location. The FrzCD binding to the nucleoid occur in a DNA-sequence independent manner and leads to the formation of multiple distributed clusters that explore constrained areas. This organization might be required for cooperative interactions between clustered receptors as observed in membrane-bound chemosensory arrays.\n\nAUTHOR SUMMARYIn this work, we show that the cytoplasmic chemoreceptor of the Frz chemosensory system, FrzCD, does not bind the cytoplasmic membrane like most MCPs but bind the bacterial nucleoid directly, thus forming distributed protein clusters also containing the Frz kinase. In vitro and in vivo experiments show that DNA-binding is not sequence-specific and is mediated by a basic aminoacid sequence of the FrzCD N-terminal domain. The deletion of this motif abolishes FrzCD DNA-binding and cooperativity in the response to signals. This work shows the importance of the nucleoid in the organization and functioning of cytoplasmic signaling systems in bacteria.

microbiology↗

bioRxiv2017

A Tunable Protein Oscillator Controls Directional Movements In Myxococcus xanthus

Dynamic control of cell polarity is of critical importance for many aspects of cellular development and motility. In Myxococcus xanthus, a G-protein and its cognate GTPase-activating protein establish a polarity axis that defines the direction of movement of the cell and which can be rapidly inverted by the Frz chemosensory system. Although vital for collective cell behaviours, how Frz triggers this switch has remained unknown. Here, we use genetics, imaging and mathematical modelling to show that Frz controls polarity reversals via a gated relaxation oscillator. FrzX, which we newly identify as the primary Frz output, provides the gating and thus acts as the trigger for reversals. Slow relocalisation of the polarity protein RomR then creates a refractory period during which another switch cannot be triggered. A secondary Frz output, FrzZ, decreases this delay allowing rapid reversals when required. This architecture thus results in a highly tunable switch that allows a wide range of motility responses.

microbiology↗