- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Ion Transport and Channel Regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Nerve injury and regeneration
- Genetics and Neurodevelopmental Disorders
- Glioma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Neuroendocrine regulation and behavior
- ATP Synthase and ATPases Research
- Tryptophan and brain disorders
- Neurological Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Transcranial Magnetic Stimulation Studies
- Anesthesia and Neurotoxicity Research
- Molecular Sensors and Ion Detection
- Epilepsy research and treatment
- Biochemical effects in animals
Aix-Marseille Université
2016-2025
Inserm
2016-2025
Institut de Neurobiologie de la Méditerranée
2016-2025
University of Helsinki
2016-2025
Centre de Recherche et d’Enseignement de Géosciences de l’Environnement
2022-2023
Collège de France
2022-2023
Institut de Recherche pour le Développement
2022-2023
Centre National de la Recherche Scientifique
2022-2023
Helsinki Art Museum
2021
University of Pennsylvania
2017-2018
Changes in chloride (Cl − ) homeostasis may be involved the generation of some epileptic activities. In this study, we asked whether Cl homeostasis, and thus GABAergic signaling, is altered tissue from patients with mesial temporal lobe epilepsy associated hippocampal sclerosis. Slices prepared human generated a spontaneous interictal-like activity that was initiated subiculum. Records minority subicular pyramidal cells revealed depolarizing GABA A receptor-mediated postsynaptic events,...
Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl- regulation, which can lead a suppression fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases excitability through conjunction mechanisms that include regulation the efficacy transmission. Here, we show exposure rat hippocampal slice cultures acute slices exogenous BDNF or neurotrophin-4 produces TrkB-mediated fall in...
GABA-mediated fast-hyperpolarizing inhibition depends on extrusion of chloride by the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained interictal-like activity in hippocampal slices downregulates KCC2 mRNA and protein expression CA1 pyramidal neurons, which leads to a reduced capacity for neuronal Cl- extrusion. This effect is mediated endogenous BDNF acting tyrosine receptor kinase B (TrkB), with down-stream cascades involving both Shc/FRS-2 (src homology 2 domain...
Dendritic spines are small protrusions along dendrites where the postsynaptic components of most excitatory synapses reside in mature brain. Morphological changes these actin-rich structures associated with learning and memory formation. Despite pivotal role actin cytoskeleton spine morphogenesis, little is known about mechanisms regulating filament polymerization depolymerization dendritic spines. We show that filopodia-like precursors elongate through at both filopodia tip root. The GTPase...
Epileptic discharges in the neocortex surrounding human gliomas are initiated by GABAergic interneurons through alterations of chloride homeostasis pyramidal cells.
Spontaneous transients of correlated activity are a characteristic feature immature brain structures, where they thought to be crucial for the establishment precise neuronal connectivity. Studies on experimental animals have shown that this kind early in cortical structures is composed long-lasting, intermittent network events, which undergo developmental decline closely paralleled by maturation GABAergic inhibition. In order examine whether similar events occur human cortex, we performed...
Abstract Intracellular Cl – plays a key role in cellular volume regulation, cell cycle control and shaping the polarity of inhibitory postsynaptic responses mediated by anion‐permeable GABA glycine receptors. In this study, we have investigated expression patterns members cation‐chloride cotransporters (CCCs), including K‐Cl KCC1‐4 Na‐K‐2 cotranporter NKCC1 during rodent embryonic brain development. At time neurogenesis (embryonic days; E12.5–14.5), KCC1 was only detectable developing...
Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential Parkinson's disease. Soluble GFLs bind to a ligand-specific glycosylphosphatidylinositol-anchored coreceptor (GDNF receptor α) signal through the tyrosine kinase RET. In this paper, we show that all immobilized matrix-bound GFLs, except persephin, use fundamentally different receptor. They interact syndecan-3, transmembrane...
DURING BRAIN DEVELOPMENT, THERE IS A PROGRESSIVE REDUCTION OF INTRACELLULAR CHLORIDE ASSOCIATED WITH SHIFT IN GABA POLARITY: depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range animal species, brain structures preparations, is thought to play an important role activity-dependent formation modulation functional circuits. sequence also considerably reinforced recently...
Injectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable biodegradable hydrogel based on amphiphilic PNIPAAm-b-PLA-b-PEG-b-PLA-b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The formation at around 30 °C was demonstrated to be mediated intermicellar bridging through the PEG central block. Such a result...
Identification of the molecular mechanisms that enable synchronous firing CA1 pyramidal neurons is central to understanding functional properties this major hippocampal output pathway. Using microfluorescence measurements intraneuronal pH, in situ hybridization, as well intracellular, extracellular, and K+-sensitive microelectrode recordings, we show now capability for gamma-frequency (20-80 Hz) response high-frequency stimulation (HFS) emerges abruptly rat hippocampus at approximately...
A hallmark in the development of GABAergic neurotransmission is switch GABA(A)-mediated responses from depolarizing to hyperpolarizing. This occurs due a gradual decrease intracellular concentration chloride caused by functional expression neuron-specific K-Cl cotransporter KCC2. Whether mere increase amount KCC2 protein rate-limiting step vivo, or further activation otherwise nonfunctional required, not clear. Imposing fixed Cl(-) load via patch pipette we measured resultant...
Abstract Postsynaptic γ‐aminobutyric acid (GABA) A ‐mediated responses switch from depolarizing to hyperpolarizing during postnatal development of the rodent hippocampus. This is attributable a decrease in concentration intracellular chloride set by expression neuron‐specific K + ‐Cl − co‐transporter, KCC2. recent vitro study [Ganguly et al . (2001) Cell , 105, 521–532] showed that KCC2 may be under trophic control GABA receptor‐mediated transmission. Here we have studied developmental...
A shift of GABA<sub>A</sub>-mediated responses from hyperpolarizing to depolarizing after neuronal injury leads increase in [Ca<sup>2+</sup>]<sub>i</sub>. In addition, central neurons become dependent on BDNF for survival. Whether these two mechanisms are causally interrelated is an open question. Here, we show lesioned CA3 hippocampal <i>in vitro</i> and axotomized corticospinal vivo</i> that posttraumatic downregulation the neuron-specific K–Cl cotransporter KCC2 intracellular chloride...
A major event in the maturation of CNS GABAergic transmission is qualitative change GABA -mediated responses from depolarizing to hyperpolarizing. In cortical regions, this attributed increased expression potassium chloride cotransporter 2b (KCC2b), main isoform neuron-specific K-Cl KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate KCC2b promoter. Here we demonstrate immature hippocampal neurons BDNF robustly induces ERK1/2 (extracellular...
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for fast hyperpolarizing actions of inhibitory neurotransmitters. gene codes two isoforms, KCC2a and KCC2b, which differ in their N termini. relative expression cellular distribution protein isoforms are unknown. Here, we characterize an antibody against isoform show that a previously described is specific KCC2b (Hubner, C. A., Stein, V., Hermans-Borgmeyer, I., Meyer, T., Ballanyi, K.,...