A5085062831- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Botulinum Toxin and Related Neurological Disorders
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Biochemical and Structural Characterization
- Vestibular and auditory disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Anesthesia and Neurotoxicity Research
- Neurogenesis and neuroplasticity mechanisms
- Mosquito-borne diseases and control
- Cancer Treatment and Pharmacology
- Retinal Development and Disorders
- Pain Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Hereditary Neurological Disorders
- Blood properties and coagulation
- RNA Research and Splicing
- Streptococcal Infections and Treatments
- Nerve injury and regeneration
Centre National de la Recherche Scientifique
2007-2024
Institut des Neurosciences Cellulaires et Intégratives
2010-2023
Université de Strasbourg
2013-2023
Duke University
2000-2005
Duke University Hospital
2000-2005
Duke Medical Center
2000-2005
Marine Biological Laboratory
2005
Inserm
2004
Laboratoire de Neurobiologie Cellulaire et Moléculaire
1997-1999
Institut de Biologie Physico-Chimique
1996
Significance The inferior olive, one of the major source inputs to cerebellum, sends climbing fibers Purkinje cells, key processing units cerebellar-dependent motor control. Using an optogenetic strategy, we demonstrate that cells disinhibit their climbing-fiber afferents via a poly-synaptic circuit. These findings identify functional closed-loop organization in olivo-cerebellar circuits is potentially important for cerebellar learning.
Abstract Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However journey, from bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination CNS using human primary monocytes, cerebral organoids derived embryonic stem cells, organotypic mouse cerebellar slices, xenotypic human-zebrafish model, fetus brain samples. We find...
Synapsins are a family of neuron-specific phosphoproteins that regulate neurotransmitter release by associating with synaptic vesicles. consist series conserved and variable structural domains unknown function. We performed systematic structure-function analysis the various synapsin assessing actions fragments on release, presynaptic ultrastructure, biochemical interactions synapsin. Injecting peptide derived from domain A into squid giant terminal inhibited in phosphorylation-dependent...
The mossy fiber (MF)–granule cell (GC) pathway conveys multiple modalities of information to the cerebellar cortex, converging on Purkinje cells (PC), sole output cortex. Recent in vivo experiments have shown that activity GCs varies from tonic firing at a few hertz phasic bursts >500 Hz. However, responses parallel (PF)–PC synapses this wide range input frequencies are unknown, and there is controversy regarding several frequency-related parameters transmission synapse. We performed...
Aging weakens memory functions. Exposing healthy rodents or pathological rodent models to environmental enrichment (EE) housing improves their cognitive functions by changing neuronal levels of excitation, cellular signaling, and plasticity, notably in the hippocampus. At molecular level, brain derived-neurotrophic factor (BDNF) represents an important player that supports EE-associated changes. EE facilitation learning was also shown correlate with chromatin acetylation It is not known,...
The segregation of the readily releasable pool synaptic vesicles (RRP) in sub-pools that are differentially poised for exocytosis shapes short-term plasticity. However, frequency-dependent mobilization these is poorly understood. Using slice recordings and modeling activity at cerebellar granule cell to Purkinje synapses mice, we describe two RRP can be recruited upon ultrafast changes stimulation frequency. We show low-frequency stimulations, a first sub-pool gradually silenced, leading...
Neurotransmitter release is a highly efficient secretory process exhibiting resistance to fatigue and plasticity attributable the existence of distinct pools synaptic vesicles (SVs), namely readily releasable pool reserve from which can be recruited after activity. Synaptic in are thought reversibly tethered actin-based cytoskeleton by synapsins, family vesicle-associated phosphoproteins that have been shown play role formation, maintenance, regulation operate during post-docking step...
Rho, Rac, and Cdc42 monomeric GTPases are well known regulators of the actin cytoskeleton phosphoinositide metabolism have been implicated in hormone secretion endocrine cells. Here, we examine their possible implication Ca<sup>2+</sup>-dependent exocytosis neurotransmitters. Using subcellular fractionation procedures, found that RhoA, RhoB, Rac1, present rat brain synaptosomes; however, only Rac1 was associated with highly purified synaptic vesicles. To determine function these GTPases,...
Epsilon toxin (ET) produced by C. perfringens types B and D is a highly potent pore-forming toxin. ET-intoxicated animals express severe neurological disorders that are thought to result from the formation of vasogenic brain edemas indirect neuronal excitotoxicity. The cerebellum predilection site for ET damage. has been proposed bind glial cells such as astrocytes oligodendrocytes. However, possibility binds attacks neurons remains an open question. Using specific anti-ET mouse polyclonal...
Epsilon toxin (ET) is produced by Clostridium perfringens types B and D causes severe neurological disorders in animals. ET has been observed binding to white matter, suggesting that it may target oligodendrocytes. In primary cultures containing oligodendrocytes astrocytes, we found (10−9 M 10−7 M) binds oligodendrocytes, but not astrocytes. induces an increase extracellular glutamate, produces oscillations of intracellular Ca2+ concentration These effects occurred without any change the...
Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease mainly characterized by motor incoordination because of progressive cerebellar degeneration. SCA7 caused polyglutamine expansion in ATXN7, a subunit the transcriptional coactivator SAGA, which harbors histone modification activities. Polyglutamine expansions specific proteins are also responsible for SCA1-SCA3, SCA6, and SCA17; however, converging diverging pathomechanisms remain poorly understood. Using new...
Information processing by cerebellar molecular layer interneurons (MLIs) plays a crucial role in motor behavior. MLI recruitment is tightly controlled the profile of short-term plasticity (STP) at granule cell (GC)-MLI synapses. While GCs are most numerous neurons brain, STP diversity GC-MLI synapses poorly documented. Here, we studied how single MLIs recruited their distinct GC inputs during burst firing. Using slice recordings individual mice, revealed four classes connections segregated...
The role of small GTPases the Rho family in synaptic functions has been addressed by analyzing effects lethal toxin (LT) from<i>Clostridium sordellii</i> strain IP82 (LT82) on neurotransmitter release at evoked identified synapses buccal ganglion <i>Aplysia.</i> LT82 is a large monoglucosyltranferase that uses UDP-glucose as cofactor and glucosylates Rac (a GTPase related to Rho), Ras, Ral, Rap (three Ras family). Intraneuronal application LT (50 nm) rapidly inhibits acetylcholine (ACh)...
ABSTRACT Rab3 is a monomeric GTP-binding protein associated with secretory vesicles which has been implicated in the control of regulated exocytosis. We have exploited mutant proteins to investigate function process neurotransmitter release from Aplysia neurons. A GTPase-deficient was found inhibit acetylcholine suggesting that GTP hydrolysis by rate-limiting exocytosis process. This effect abolished mutation effector domain, and required association membranes. In order determine step at...
Tetanus toxin (TeTX) is a dichain protein that blocks neuroexocytosis, an action attributed previously to Zn2+-dependent proteolysis of synaptobrevin (Sbr) by its light chain (LC). Herein, cleavage Sbr in rat cerebrocortical synaptosomes was shown be minimized captopril, inhibitor certain metallo-endoproteases, whereas this agent only marginally antagonized the inhibition noradrenaline release, implicating second toxin. This hypothesis proven preparing three mutants (H233A, E234A, H237A) LC...
Phospholipids (PLs) are asymmetrically distributed at the plasma membrane. This asymmetric lipid distribution is transiently altered during calcium-regulated exocytosis, but impact of this transient remodeling on presynaptic function currently unknown. As phospholipid scramblase 1 (PLSCR1) randomizes PL between two leaflets membrane in response to calcium activation, we set out determine its role neurotransmission. We report here that PLSCR1 expressed cerebellar granule cells (GrCs) and...
The Rab3 proteins are monomeric GTP-binding associated with secretory vesicles. In their active GTP-bound state, involved in the regulation of hormone secretion and neurotransmitter release. This action is thought to involve specific effectors, including two Ca2+-binding proteins, Rabphilin Rim. acts late exocytotic process, a cell domain which intracellular Ca2+ concentration susceptible rapid changes. Therefore, we examined possible Ca2+-dependency regulatory wild-type on neuroexocytosis...
Synaptic transmission can be described as a stochastic quantal process defined by three main parameters: N, the number of functional release sites; P, probability; and Q, quantum response. Many changes in synaptic strength that are observed during expression short term plasticity rely on modifications P. Regulation N has been also suggested. We have investigated at identified cholinergic inhibitory Aplysia synapses cellular mechanism post-tetanic potentiation (PTP) expressed under control...
Abstract Deletion of both alleles the P/Q‐type Ca 2+ ‐channel v 2.1(α 1A ) subunit gene in mouse leads to severe ataxia and early death. Using cerebellar slices obtained from 10 15 postnatal days mice cultured for at least 3 weeks vitro , we have analysed synaptic alterations produced by genetically ablating ‐channels, compared them with effect pharmacological inhibition P/Q‐ or N‐type channels on wild‐type littermate mice. Analysis spontaneous currents recorded Purkinje cells (PCs)...
Repetitive firing of neurons at a low frequency often leads to decrease in synaptic strength. The mechanism this low-frequency depression (LFD) is poorly understood. Here, LFD was studied Aplysia cholinergic synapses. absence significant change the paired-pulse ratio during LFD, together with facts that neither time course nor extent were affected by initial release probability, suggests not related depletion ready-to-fuse vesicles (SVs) or but results from silencing subpopulation sites. A...