A5062051578- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Heme Oxygenase-1 and Carbon Monoxide
- Autoimmune Neurological Disorders and Treatments
- Ion channel regulation and function
- Neural dynamics and brain function
- Amino Acid Enzymes and Metabolism
- Cannabis and Cannabinoid Research
- Advanced Fluorescence Microscopy Techniques
- Photoreceptor and optogenetics research
- Tryptophan and brain disorders
- Alcohol Consumption and Health Effects
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- Neurobiology and Insect Physiology Research
- Electrolyte and hormonal disorders
- Xenotransplantation and immune response
- Photochromic and Fluorescence Chemistry
- Energy Efficient Wireless Sensor Networks
- GDF15 and Related Biomarkers
- Calpain Protease Function and Regulation
- Advanced Chemical Physics Studies
- Advanced MEMS and NEMS Technologies
- Health, Medicine and Society
- Cell death mechanisms and regulation
Institut Interdisciplinaire de Neuroscience
2013-2024
Université de Bordeaux
2012-2024
Centre National de la Recherche Scientifique
2013-2024
Centre National pour la Recherche Scientifique et Technique (CNRST)
2020
Université de Rennes
2010
Institut des Sciences Chimiques de Rennes
2010
Électricité de France (France)
2006
Inserm
2002-2004
Canadian Nautical Research Society
2004
University College London
2003
Autoimmune synaptic encephalitides are recently described human brain diseases leading to psychiatric and neurological syndromes through inappropriate brain-autoantibody interactions. The most frequent autoimmune encephalitis is associated with autoantibodies against extracellular domains of the glutamatergic N-methyl-d-aspartate receptor, patients developing psychotic symptoms in an autoantibody titre-dependent manner. Although receptors primary target these antibodies, cellular molecular...
In the nucleus accumbens (NAc), a key structure to effects of all addictive drugs, presynaptic cannabinoid CB1 receptors (CB1Rs) and postsynaptic metabotropic glutamate 5 (mGluR5s) are principal effectors endocannabinoid (eCB)-mediated retrograde long-term depression (LTD) (eCB-LTD) at prefrontal cortex-NAc synapses. Both CB1R mGluR5 involved in cocaine-related behaviors; however, impact vivo cocaine exposure on eCB-mediated synaptic plasticity remains unknown. Electrophysiological...
The identification of circulating autoantibodies against neuronal receptors in neuropsychiatric disorders has fostered new conceptual and clinical frameworks. However, detection reliability, putative presence different diseases health have raised questions about potential pathogenic mechanism mediated by autoantibodies. Using a combination single molecule-based imaging approaches, we here ascertain the glutamate NMDA receptor (NMDAR-Ab) 20% psychotic patients diagnosed with schizophrenia...
The subunit composition of synaptic NMDA receptors (NMDAR), such as the relative content GluN2A- and GluN2B-containing receptors, greatly influences glutamate transmission. Receptor co-agonists, glycine D-serine, have intriguingly emerged potential regulators receptor trafficking in addition to their requirement for its activation. Using a combination single-molecule imaging, biochemistry electrophysiology, we show that D-serine availability at rat hippocampal glutamatergic synapses regulate...
The relative content of NR2 subunits in the NMDA receptor confers specific signaling properties and plasticity to synapses. However, mechanisms that dynamically govern retention synaptic NMDARs, particular 2A-NMDARs, remain poorly understood. Here, we investigate dynamic interaction between C termini proteins containing PSD-95/Discs-large/ZO-1 homology (PDZ) scaffold at single molecule level by using high-resolution imaging. We report a biomimetic divalent competing ligand, mimicking last 15...
Significance Dopamine receptor signaling in the brain participates memory encoding through regulation of glutamatergic signaling. Here we provide evidence that single dopamine D1 receptors are highly dynamic at surface hippocampal neurons. In addition, these receptors, together with NMDA form clusters vicinity glutamate synapses, providing a strategically located reservoir pool from which they can be laterally redistributed during synaptic adaptations. The plasma membrane and dynamics thus...
Astrocytes constantly adapt their ramified morphology in order to support brain cell assemblies. Such plasticity is partly mediated by ion and water fluxes, which rely on the channel aquaporin-4 (AQP4). The mechanism this locally contributes process dynamics has remained elusive. Using a combination of single-molecule calcium imaging approaches, we here investigated hippocampal astrocytes dynamic distribution AQP4 isoforms M1 M23. Surface AQP4-M1 formed small aggregates that contrast with...
Retroviral protein, expressed in patients with psychotic disorders, corrupts the development of excitatory synapses and behavior.
Abstract Autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR-Ab) are pathogenic immunoglobulins detected in patients suffering from NMDAR encephalitis. NMDAR-Ab alter membrane trafficking, synaptic transmission and neuronal network properties, leading to neurological psychiatric symptoms patients. Patients often have very little damage but rapid massive (treatment-responsive) brain dysfunctions related an unknown early mechanism of NMDAR-Ab. Our understanding this...
Abstract Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to environment. The corticosterone-induced adaptations partly rely on changes in NMDAR signalling, although cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging electrophysiological approaches neurons, that corticosterone...
Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine receptor-mediated interplay at synapse remain poorly understood. Among mechanisms proposed to aggregate D1R synapses, direct interaction between scaffold protein PSD95 or with NMDA (NMDAR) proposed. To tackle this question we here...
Hippocampal pyramidal neurons are characterized by a unique arborization subdivided in segregated dendritic domains receiving distinct excitatory synaptic inputs with specific properties and plasticity rules that shape their respective contributions to integration action potential firing. Although the basal regulation plastic range of proximal distal synapses known be different, composition nanoscale organization key proteins at these remains largely elusive. Here we used superresolution...
Activity-dependent modulations of N-methyl-D-aspartate glutamate receptor (NMDAR) trapping at synapses regulate excitatory neurotransmission and shape cognitive functions. Although NMDAR synaptic destabilization has been associated with severe neurological psychiatric conditions, tuning to assess its clinical relevance for the treatment brain conditions remains a challenge. Here, we report that ketamine (KET) other clinically relevant open channel blockers (OCBs) promote interactions between...
Circulating autoantibodies directed against extracellular domains of the glutamatergic N-methyl-D-aspartate receptors (NMDAR-Ab) elicit psychotic symptoms in humans and behavioral deficits animal models. Recent advances suggest that NMDAR-Ab exert their pathogenic action by altering trafficking NMDAR, which results a synaptic NMDAR hypofunction consistent with consensual hypothesis disorders. Yet, dysfunction dopaminergic signaling is also proposed to be at core Since dopamine D1 (D1R) form...
Signaling via N-methyl-d-aspartate receptors (NMDARs) is critical for the maturation of glutamatergic synapses, partly through a developmental switch from immature synapses expressing primarily GluN2B- and GluN3A-containing subtypes to GluN2A-rich mature ones. This subunit thought underlie synaptic stabilization NMDARs necessary neural network consolidation. However, cellular mechanisms controlling NMDAR exchange remain unclear. Using combination single-molecule confocal imaging biochemical...
Recent developments in single-molecule imaging have revealed many biological mechanisms, providing high spatial and temporal resolution maps of molecular events. In neurobiology, these techniques unveiled that plasma membrane neurotransmitter receptors transporters laterally diffuse at the surface cultured brain cells. The photostability bright nanoprobes, such as quantum dots (QDs), has given access to receptor tracking over long periods time with a resolution. However, our knowledge been...
Abstract A dysfunction of the glutamatergic transmission, especially NMDA receptor (NMDAR), constitutes one main biological substrate psychotic disorders, such as schizophrenia. The NMDAR signaling hypofunction, through genetic and/or environmental insults, would cause a neurodevelopmental myriad molecular, cellular, and network alterations that persist throughout life. Yet, mechanisms underpinning dysfunctions remain elusive. Here, we compared membrane trafficking in three gold-standard...
Fas ligand expression by cells of the vessel wall has been proposed to play a role in normal and pathologic conditions. Genetic engineering vascularized organs for endothelial cell (EC) FasL could protect endothelium underlying tissues from infiltrating Fas+ leukocytes. Nevertheless, endogenous ECs different species potential deleterious effects enforced are largely unknown. In human ECs, levels FLICE/caspase 8-inhibitory protein (FLIP) have shown control apoptosis mediated Fas.Cell surface...
Heme oxygenase-1 (HO-1) expression protects cells from a variety of cellular insults and inhibits inflammation. However, its role in the regulation immune responses has not yet been clearly established. We generated HO-1 transgenic rats to directly test impact on different mechanisms. To temporally control HO-1, we used one-plasmid tetracycline (tet)-inducible system. This plasmid contains H-2K b promoter, which transcribes tet transactivator (tTA) human cDNA is obtained absence...