A5020100632- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- Advanced Electron Microscopy Techniques and Applications
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- 3D Printing in Biomedical Research
- Graphene and Nanomaterials Applications
- Force Microscopy Techniques and Applications
- Ion channel regulation and function
- Advanced Memory and Neural Computing
- Optical Imaging and Spectroscopy Techniques
- Nicotinic Acetylcholine Receptors Study
- Advanced Optical Sensing Technologies
- Nanoparticles: synthesis and applications
- Click Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- Gastroesophageal reflux and treatments
- Electrospun Nanofibers in Biomedical Applications
- Advanced Sensor and Energy Harvesting Materials
- Near-Field Optical Microscopy
Italian Institute of Technology
2014-2024
Université de Bordeaux
2009
Centre National de la Recherche Scientifique
2009
Scuola Internazionale Superiore di Studi Avanzati
2002-2004
AREA Science Park
2002
Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased GABAA receptors (GABAARs) at synapses by promoted exocytosis. However, the molecular mechanisms that enhance clustering postsynaptic GABAARs during iLTP remain obscure. Here we demonstrate chemically induced (chem-iLTP), are immobilized and confined synapses, as revealed single-particle tracking individual in cultured hippocampal neurons. Chem-iLTP expression requires synaptic recruitment scaffold protein gephyrin...
Nanoparticles (NPs) are increasingly used in biomedical applications, but the factors that influence their interactions with living cells need to be elucidated. Here, we reveal role of NP surface charge determining neuronal and electrical responses. We discovered negatively charged NPs administered at low concentration (10 nM) interact membrane synaptic cleft, whereas positively neutrally never localize on neurons. This effect is shape material independent. The presence cell membranes...
Gephyrin is a key scaffold protein mediating the anchoring of GABAA receptors at inhibitory synapses. Here, we exploited superresolution techniques combined with proximity-based clustering analysis and model simulations to investigate single-molecule gephyrin reorganization during plasticity synapses in mouse hippocampal cultured neurons. This approach revealed that, expression LTP, increase density postsynaptic sites associated promoted formation nanodomains. We demonstrate that...
Abstract The generation of 3D networks primary neurons is a big challenge in neuroscience. Here, novel method presented for neuronal culture on superhydrophobic (SH) substrates. How nano‐patterned SH devices stimulate to build investigated. Scanning electron microscopy and confocal imaging show that soon after plating neurites adhere the nanopatterned pillar sidewalls they are subsequently pulled between pillars suspended position. These display an enhanced survival rate compared standard...
The induction of synaptic plasticity at an individual dendritic glutamatergic spine can affect neighboring spines. This local modulation generates microdomains believed to expand the neuronal computational capacity. Here, we investigate whether also occur between synapses and adjacent GABAergic synapses. We find that long-term potentiation causes depression nearby inhibitory (within 3 μm), whereas more distant ones are potentiated. Notably, L-type calcium channels calpain required for this...
The time course of synaptic currents is a crucial determinant rapid signaling between neurons. Traditionally, the mechanisms underlying shape signals are classified as pre and postsynaptic. Over last two decades, an extensive body evidence indicated that critically shaped by neurotransmitter which encompasses several phenomena including pre- postsynaptic ones. In particular, agonist transient depends on release mechanisms, diffusion within cleft, spill-over to extrasynaptic space, uptake...
The lateral mobility of neurotransmitter receptors has been shown to tune synaptic signals. Here we report that GABAA (GABAARs) can diffuse between adjacent dendritic GABAergic synapses in long-living desensitized states, thus laterally spreading "activation memories" inhibitory synapses. Glutamatergic activity limits this inter-synaptic diffusion by trapping GABAARs at excitatory This novel form activity-dependent hetero-synaptic interplay is likely modulate signaling.
Abstract The variability of quantal size depends on both presynaptic (profile the neurotransmitter concentration in cleft) and postsynaptic (number gating properties receptors) factors. Here we have examined possibility that at nonsaturated synapses cultured hippocampal neurons, changes transmitter peak its clearance from synaptic cleft may influence spontaneous miniature GABAergic currents (mIPSCs). We found that, contrast to slow‐off GABA A receptor antagonist bicuculline, fast‐off...
Tonic inhibition plays a crucial role in regulating neuronal excitability because it sets the threshold for action potential generation and integrates excitatory signals. currents are known to be largely mediated by extrasynaptic γ-aminobutyric acid type A (GABAA) receptors that persistently activated submicromo-lar concentrations of ambient GABA. We recently reported that, cultured hippocampal neurons, clustering synaptic GABAA significantly affects transmission (Petrini, E. M., Zacchi, P.,...
To reach the open state, GABA A receptor (GABA R) is assumed to bind two agonist molecules. Although it currently believed that R could also operate in monoliganded gating properties of singly bound are poorly understood and their physiological role still obscure. In present study, we characterize for first time Rs by using a mutagenesis approach propose contribute shaping synaptic responses. At saturating concentrations, currents mediated recombinant with single functional binding site...
As is known, carbon nanotubes favor cell growth in vitro, although the underlying mechanisms are not yet fully elucidated. In this study, we explore hypothesis that electrostatic fields generated at interface between nonexcitable cells and appropriate scaffold might by tuning their membrane potential. We focused on primary human fibroblasts grown electrospun polymer fibers (poly(lactic acid)─PLA) with embedded multiwall (MWCNTs). The MWCNTs were functionalized either
Abstract Learning and memory are known to depend on synaptic plasticity. Whereas the involvement of plastic changes at excitatory synapses is well established, plasticity mechanisms inhibitory only start be discovered. Extracellular proteolysis a key factor in glutamatergic but nothing about its role GABAergic synapses. We reveal that pharmacological inhibition MMP3 activity or genetic knockout Mmp3 gene abolishes induction postsynaptic iLTP. Moreover, application exogenous active mimics...
Kainate receptors (KARs) mediate postsynaptic currents with a key impact on neuronal excitability. However, the molecular determinants controlling KAR localization and stabilization are poorly understood. Here, we exploit optogenetic single-particle tracking approaches to study role of conformational states induced by glutamate binding lateral mobility at synapses. We report that following binding, KARs readily reversibly trapped glutamatergic synapses through increased interaction...
The single-photon timing and sensitivity performance the imaging ability of asynchronous-readout avalanche diode (SPAD) array detectors have opened up enormous perspectives in fluorescence (lifetime) laser scanning microscopy (FLSM), such as super-resolution image high-information content fluctuation spectroscopy. However, strengths these FLSM techniques depend on many different characteristics detector, dark noise, photon-detection efficiency, after-pulsing probability, optical cross talk,...
Speed and reliability of synaptic transmission are essential for information coding in neuronal networks require the presence clustered neurotransmitter receptors at plasma membrane precise apposition to presynaptic terminals. Receptor clusterization is result highly regulated processes involving functional structural proteins. Among elements, microtubules known play a crucial role anchoring gamma-aminobutyric acid, type A (GABA(A)) receptors. Here we show that microtubule depolymerization...
Fluorescence labeling of difficult to access protein sites, e.g., in confined compartments, requires small fluorescent labels that can be covalently tethered at well-defined positions with high efficiency. Here, we report site-specific the extracellular domain γ-aminobutyric acid type A (GABA-A) receptor subunits by genetic code expansion (GCE) unnatural amino acids (ncAA) combined bioorthogonal click-chemistry tetrazine dyes HEK-293-T cells and primary cultured neurons. After optimization...
The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs) work together with synaptic adhesion molecule neuroligin 2 (NL2) to regulate formation in different subcellular compartments. investigated mice (“γ2 knockdown mice”) an engineered allele GABAAR γ2 subunit gene which produced a mosaic expression GABAARs neighboring neurons, causing strong imbalance inhibition. Deletion did not abolish or targeting NL2...
Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed plasticity. Although the molecular mechanisms underlying glutamatergic plasticity have been extensively investigated described, those responsible for only beginning to be unveiled. In this framework, ultrastructural of synapses during poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron (HRSEM)...
Glioblastoma cancer stem-like cells seeded on substrates exhibiting surface potential differences, undergo differentiation due to the forced hyperpolarization of membrane at cell/substrate interface.