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10 results on '"MESH : Synaptic Transmission"'

1. Preface: Cholinergic Mechanisms

Author

Prado, Marco, Marchot, Pascale, Silman, Israel, Prado, Marco A.M., Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of Neurobiology, Weizmann Institute of Science, Weizmann Institute of Science [Rehovot, Israël], Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Architecture et fonction des macromolécules biologiques ( AFMB ), and Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA )

Subjects
0301 basic medicine, MESH: Neurotoxicity Syndromes, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Protein biomarkers, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cholinergic Agents, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Synaptic Transmission, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Biochemistry, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Cholinergic synapse, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], media_common, Developmental neurotoxicity, MESH : Synaptic Transmission, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH : Neurotoxicity Syndromes, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cholinergic neurotransmission, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neurotoxicity Syndromes, Psychology, media_common.quotation_subject, education, Neuromuscular Junction, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Behavior, Addictive, MESH: Synaptic Transmission, Animals, Humans, MESH: Cholinergic Agents, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH : Behavior, Addictive, MESH : Acetylcholine, MESH : Cholinergic Agents, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Humans, MESH: Acetylcholine, Addiction, MESH : Humans, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Acetylcholine, Behavior, Addictive, 030104 developmental biology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cholinesterase genes, MESH : Neuromuscular Junction, Cholinergic, MESH : Animals, MESH: Neuromuscular Junction, Cholinergic mechanisms, Neuroscience, 030217 neurology & neurosurgery, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience; This special issue is a companion to the meeting 'XVth International Symposium on Cholinergic Mechanisms', and is edited by Israel Silman, Marco Prado and Pascale Marchot. In the review articles, renowned researchers in the field capture key mechanisms of cholinergic neurotransmission, from genomic amplification of cholinesterase genes, splicing and post-translational modifications; features of the neuromuscular junction, implications of cholinergic circuitry that are relevant to addiction, anxiety and mood, to preclinical models, protein biomarkers, and clinical findings that are relevant to pathology, for example, developmental neurotoxicity. The broad variety of features reflects the impact of cholinergic mechanisms on many physiological events and emphasizes the importance of research in this area. This is the Preface for the special issue XVth International Symposium on Cholinergic Mechanisms.

Published
2017
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2. A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential

Author

Delphine Rigault, Francine Acher, Nadia Oueslati, Hervé Daniel, Marianne Amalric, Isabelle Brabet, Jean-Philippe Pin, Heather McLean, Hugues-Olivier Bertrand, Tiphanie Courtiol, Bruno Vilar, Thomas Bessiron, Cyril Goudet, Thierry Deltheil, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Accelrys SARL, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS) - Université Montpellier 2 - Sciences et Techniques (UM2) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Montpellier 1 (UM1) - Université de Montpellier (UM), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU) - Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11) - Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Patch-Clamp Techniques, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Antiparkinson Agents, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, MESH : Dose-Response Relationship, Drug, Pharmacology, Ligands, Receptors, Metabotropic Glutamate, Synaptic Transmission, Biochemistry, MESH: Mice, Knockout, MESH: Dose-Response Relationship, Drug, Antiparkinson Agents, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, MESH: Structure-Activity Relationship, MESH : Structure-Activity Relationship, Excitatory Amino Acid Agonists, MESH: Ligands, MESH: Animals, MESH : Patch-Clamp Techniques, Receptor, Mice, Knockout, MESH : Synaptic Transmission, MESH : Ligands, 0303 health sciences, Molecular Structure, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, MESH : Rats, Chemistry, Metabotropic glutamate receptor 4, MESH : Receptors, Metabotropic Glutamate, Glutamate receptor, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Glutamate binding, MESH : Antiparkinson Agents, MESH : Phosphinic Acids, Recombinant Proteins, MESH : Mutagenesis, Site-Directed, MESH: Mutagenesis, Site-Directed, MESH: HEK293 Cells, Metabotropic glutamate receptor 1, MESH: Phosphinic Acids, Biotechnology, Agonist, MESH: Rats, MESH : Recombinant Proteins, medicine.drug_class, MESH : Male, MESH: Molecular Structure, MESH : Rats, Wistar, Structure-Activity Relationship, 03 medical and health sciences, MESH : Mice, MESH: Patch-Clamp Techniques, Genetics, medicine, MESH: Synaptic Transmission, Animals, Humans, Rats, Wistar, MESH: Receptors, Metabotropic Glutamate, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : Excitatory Amino Acid Agonists, Binding Sites, MESH: Humans, Dose-Response Relationship, Drug, MESH : Humans, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Rats, Wistar, Phosphinic Acids, MESH: Male, Rats, MESH : HEK293 Cells, HEK293 Cells, Metabotropic receptor, MESH: Binding Sites, Metabotropic glutamate receptor, Mutagenesis, Site-Directed, MESH : Mice, Knockout, MESH : Animals, MESH: Excitatory Amino Acid Agonists, MESH : Molecular Structure, MESH : Binding Sites, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract

International audience; Metabotropic glutamate (mGlu) receptors are promising targets to treat numerous brain disorders. So far, allosteric modulators are the only subtype selective ligands, but pure agonists still have strong therapeutic potential. Here, we aimed at investigating the possibility of developing subtype-selective agonists by extending the glutamate-like structure to hit a nonconsensus binding area. We report the properties of the first mGlu4-selective orthosteric agonist, derived from a virtual screening hit, LSP4-2022 using cell-based assays with recombinant mGlu receptors [EC(50): 0.11 ± 0.02, 11.6 ± 1.9, 29.2 ± 4.2 μM (n>19) in calcium assays on mGlu4, mGlu7, and mGlu8 receptors, respectively, with no activity at the group I and -II mGlu receptors at 100 μM]. LSP4-2022 inhibits neurotransmission in cerebellar slices from wild-type but not mGlu4 receptor-knockout mice. In vivo, it possesses antiparkinsonian properties after central or systemic administration in a haloperidol-induced catalepsy test, revealing its ability to cross the blood-brain barrier. Site-directed mutagenesis and molecular modeling was used to identify the LSP4-2022 binding site, revealing interaction with both the glutamate binding site and a variable pocket responsible for selectivity. These data reveal new approaches for developing selective, hydrophilic, and brain-penetrant mGlu receptor agonists, offering new possibilities to design original bioactive compounds with therapeutic potential.

Published
2016
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3. Synthesis and Biological Evaluation of 1-Amino-2-Phosphonomethylcyclopropanecarboxylic Acids, New Group III Metabotropic Glutamate Receptor Agonists

Author

Cyril Goudet, Hugues-Olivier Bertrand, Isabelle Brabet, Michael J. Marino, Pauline Sibille, Florence Gaven, Sébastien Lopez, Jacques Neyton, Jean-Philippe Pin, Ornella Valenti, Francine Acher, Nadia Oueslati, Marianne Amalric, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Neurology, Merck Research Laboratories, Accelrys, Laboratoire de Neurobiologie (UMR 8544) (NEURO), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Fondation de France (Parkinson committee), RETINA-France, the french National Research Agency (ANR-05-NEUR-021-01), the french ministry of Education and Research and the Centre National de la Recherche Scientifique., ANR-05-NEUR-0021,MGluRs Park,Cible thérapeutique potentielle de nouveaux ligands des récepteurs métabotropiques du glutamate du groupe III dans le traitement de la maladie de Parkinson : de la conception à l'évaluation préclinique(2005), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Cognitives [Marseille] ( LNC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Laboratoire de Neurobiologie (UMR 8544) ( NEURO ), École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), ANR PARK, ANR-05-NEUR-021-01,ANR PARK, ANR-05-NEUR-021-01, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Goudet, Cyril, and Neurosciences, neurologie et psychiatrie - Cible thérapeutique potentielle de nouveaux ligands des récepteurs métabotropiques du glutamate du groupe III dans le traitement de la maladie de Parkinson : de la conception à l'évaluation préclinique - - MGluRs Park2005 - ANR-05-NEUR-0021 - NEURO - VALID

Subjects
Male, Models, Molecular, MESH : Cell Line, Patch-Clamp Techniques, MESH: Amino Acids, MESH: Antiparkinson Agents, Molecular Conformation, MESH: Catalepsy, MESH: Rats, Sprague-Dawley, Pharmacology, Receptors, Metabotropic Glutamate, Synaptic Transmission, Basal Ganglia, Antiparkinson Agents, Rats, Sprague-Dawley, MESH: Basal Ganglia, MESH: Structure-Activity Relationship, 0302 clinical medicine, MESH : Structure-Activity Relationship, Drug Discovery, MESH: Animals, Amino Acids, MESH : Patch-Clamp Techniques, MESH : Haloperidol, Receptor, MESH : Synaptic Transmission, 0303 health sciences, MESH : Rats, Chemistry, Metabotropic glutamate receptor 4, MESH : Receptors, Metabotropic Glutamate, Metabotropic glutamate receptor 6, Stereoisomerism, MESH : Antiparkinson Agents, 3. Good health, HYDIA, MESH : Stereoisomerism, Biochemistry, Molecular Medicine, Metabotropic glutamate receptor 1, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Phosphonic Acids, MESH: Models, Molecular, Agonist, MESH: Rats, MESH : Models, Molecular, medicine.drug_class, MESH : Male, Organophosphonates, MESH: Phosphonic Acids, In Vitro Techniques, Catalepsy, MESH : Rats, Wistar, Receptors, N-Methyl-D-Aspartate, Cell Line, Injections, Structure-Activity Relationship, 03 medical and health sciences, MESH: Patch-Clamp Techniques, MESH: Synaptic Transmission, medicine, Animals, Humans, MESH: Injections, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, MESH: Receptors, Metabotropic Glutamate, MESH : Basal Ganglia, 030304 developmental biology, MESH: Receptors, N-Methyl-D-Aspartate, MESH: Molecular Conformation, MESH: Humans, MESH : Catalepsy, MESH : Humans, MESH: Rats, Wistar, medicine.disease, MESH : Injections, MESH: Stereoisomerism, MESH : Rats, Sprague-Dawley, MESH: Male, Rats, MESH: Cell Line, MESH: Haloperidol, MESH : Molecular Conformation, Metabotropic glutamate receptor, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Haloperidol, MESH : Amino Acids, MESH : Animals, MESH : Receptors, N-Methyl-D-Aspartate, 030217 neurology & neurosurgery
Abstract

International audience; Stereoisomers of 1-amino-2-phosphonomethylcyclopropanecarboxylic acid (APCPr), conformationally restricted analogues of L-AP4 (2-amino-4-phosphonobutyric acid), have been prepared and evaluated at recombinant group III metabotropic glutamate receptors. They activate these receptors over a broad range of potencies. The most potent isomer (1S,2R)-APCPr displays a similar pharmacological profile as that of L-AP4 (EC50 0.72, 1.95, >500, 0.34 microM at mGlu4, 6, 7, 8 receptors, respectively, and no effect at group I/II mGluRs). It was characterized on native receptors located in the basal ganglia (BG) where it induced a robust and reversible inhibition of synaptic transmission. It was tested in vivo in haloperidol-induced catalepsy, a model of Parkinsonian akinesia, by direct infusion in the globus pallidus of the BG. At a dose of 0.5 nmol/microL, catalepsy was significantly antagonized. This study reveals that (1S,2R)-APCPr is a potent group III mGluR agonist and confirms that these receptors may be considered as a therapeutic target in the Parkinson's disease.

Published
2007
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4. The Combined Effects of Inhibitory and Electrical Synapses in Synchrony

Author

David Golomb, Benjamin Pfeuty, Germán Mato, David Hansel, Neurophysique et physiologie du système moteur ( NPSM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Centro Atómico Bariloche [Argentine], Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] ( CONICET ) -Comisión Nacional de Energía Atómica [ARGENTINA] ( CNEA ), Instituto Balseiro [Bariloche], Comisión Nacional de Energía Atómica [ARGENTINA] ( CNEA ) -Universidad Nacional de Cuyo [Mendoza] ( UNCUYO ), Department of Physiology and Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev ( BGU ), Interdisciplinary Center for Neural Computation, The Hebrew University of Jerusalem ( HUJ ), Centre de neurophysique, physiologie, pathologie ( UMR 8119 ), Departamento de Fisica Teorica, Universidad Autonoma de Madrid ( UAM ), Laboratoire Franco-Israelien de Neurophysiologie et Neurophysique des Systèmes, Université Paris Descartes - Paris 5 ( UPD5 ), Neurophysique et physiologie du système moteur (NPSM), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Comisión Nacional de Energía Atómica [ARGENTINA] (CNEA), Comisión Nacional de Energía Atómica [ARGENTINA] (CNEA)-Universidad Nacional de Cuyo [Mendoza] (UNCUYO), Ben-Gurion University of the Negev (BGU), The Hebrew University of Jerusalem (HUJ), Centre de neurophysique, physiologie, pathologie (UMR 8119), Universidad Autonoma de Madrid (UAM), and Université Paris Descartes - Paris 5 (UPD5)

Subjects
MESH: Gap Junctions, Action Potentials, Synaptic Transmission, MESH: Synapses, Synapse, Models of neural computation, MESH : Electric Conductivity, Phase response, MESH: Animals, MESH : Dendrites, MESH: Action Potentials, Physics, MESH : Synaptic Transmission, MESH : Neural Networks (Computer), Gap Junctions, MESH: Neural Inhibition, MESH : Nonlinear Dynamics, MESH: Interneurons, MESH: Nonlinear Dynamics, MESH : Computer Simulation, medicine.anatomical_structure, Electrical Synapses, GABAergic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Gap Junctions, MESH : Synapses, Interneuron, Cognitive Neuroscience, Models, Neurological, MESH: Electric Conductivity, MESH : Interneurons, MESH: Dendrites, Inhibitory postsynaptic potential, MESH: Neural Networks (Computer), MESH: Computer Simulation, Arts and Humanities (miscellaneous), Interneurons, MESH: Models, Neurological, MESH : Action Potentials, MESH: Synaptic Transmission, medicine, Animals, MESH : Models, Neurological, Computer Simulation, Electric Conductivity, Conductance, Neural Inhibition, Dendrites, Nonlinear Dynamics, MESH: Nerve Net, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Synapses, MESH : Nerve Net, Neural Networks, Computer, MESH : Animals, Nerve Net, Neuroscience, MESH : Neural Inhibition
Abstract

Recent experimental results have shown that GABAergic interneurons in the central nervous system are frequently connected via electrical synapses. Hence, depending on the area or the subpopulation, interneurons interact via inhibitory synapses or electrical synapses alone or via both types of interactions. The theoretical work presented here addresses the significance of these different modes of interactions for the interneuron networks dynamics. We consider the simplest system in which this issue can be investigated in models or in experiments: a pair of neurons, interacting via electrical synapses, inhibitory synapses, or both, and activated by the injection of a noisy external current. Assuming that the couplings and the noise are weak, we derive an analytical expression relating the cross-correlation (CC) of the activity of the two neurons to the phase response function of the neurons. When electrical and inhibitory interactions are not too strong, they combine their effect in a linear manner. In this regime, the effect of electrical and inhibitory interactions when combined can be deduced knowing the effects of each of the interactions separately. As a consequence, depending on intrinsic neuronal proper-ties, electrical and inhibitory synapses may cooperate, both promoting synchrony, or may compete, with one promoting synchrony while the other impedes it. In contrast, for sufficiently strong couplings, the two types of synapses combine in a nonlinear fashion. Remarkably, we find that in this regime, combining electrical synapses with inhibition ampli-fies synchrony, whereas electrical synapses alone would desynchronize the activity of the neurons. We apply our theory to predict how the shape of the CC of two neurons changes as a function of ionic channel conduc-tances, focusing on the effect of persistent sodium conductance, of the firing rate of the neurons and the nature and the strength of their interac-tions. These predictions may be tested using dynamic clamp techniques.

Published
2005
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5. Bacterial Toxins and the Nervous System: Neurotoxins and Multipotential Toxins Interacting with Neuronal Cells

Author

Bernard Poulain, Michel R. Popoff, Bactéries anaérobies et Toxines, Institut Pasteur [Paris] (IP), Neurotransmission et sécrétion neuroendocrine (NSN), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Neurotransmission et sécrétion neuroendocrine ( NSN ), and Centre National de la Recherche Scientifique ( CNRS )

Subjects
Nervous system, rho GTP-Binding Proteins, actin cytoskeleton, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, MESH: Neurons, MESH : Actins, Apoptosis, Review, Toxicology, Synaptic Transmission, 0302 clinical medicine, Intestinal mucosa, MESH : Glutamic Acid, Neurotoxin, MESH: Animals, Intestinal Mucosa, toxin, Neurons, 0303 health sciences, MESH : Synaptic Transmission, MESH: Exocytosis, nervous system, MESH: Glutamic Acid, 3. Good health, Cell biology, medicine.anatomical_structure, MESH: Calcium, [SDV.TOX]Life Sciences [q-bio]/Toxicology, MESH : Monomeric GTP-Binding Proteins, Enterochromaffin cell, MESH: Intestinal Mucosa, SNARE Proteins, neurotransmitter, MESH: SNARE Proteins, Cell type, Bacterial Toxins, Neurotoxins, Glutamic Acid, MESH: Monomeric GTP-Binding Proteins, Biology, Blood–brain barrier, MESH: Actins, MESH : Neurotoxins, MESH : Intestinal Mucosa, MESH : Neurons, MESH : Exocytosis, Exocytosis, small gtpases, 03 medical and health sciences, MESH : rho GTP-Binding Proteins, medicine, MESH: Synaptic Transmission, Animals, Humans, MESH : Calcium, 030304 developmental biology, Monomeric GTP-Binding Proteins, MESH: Neurotoxins, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH: Apoptosis, MESH : Humans, neurotoxin, Actin cytoskeleton, MESH : SNARE Proteins, MESH: rho GTP-Binding Proteins, Actins, MESH: Bacterial Toxins, MESH : Bacterial Toxins, Enteric nervous system, Calcium, MESH : Animals, enterotoxin, 030217 neurology & neurosurgery, MESH : Apoptosis
Abstract

International audience; Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types including neuronal cells. Various enterotoxins interact with the enteric nervous system, for example by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, in amplification of the diarrhea, or in intestinal inflammation process. Other toxins can pass the blood brain barrier and directly act on specific neurons.

Published
2010
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6. A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions

Author

Sönke Bartling, Jeanine Koenig, Daniel Hantaï, Frédéric Chevessier, Emmanuelle Girard, Veit Witzemann, Jordi Molgó, Max-Planck-Institut für Medizinische Forschung, Max-Planck-Gesellschaft, Biologie des Jonctions Neuromusculaires Normales et Pathologiques (U686), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Abteilung medizinische Physik in der Radiologie, Deutsches Krebsforschungzentrum, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2, Centre de référence des maladies neuromusculaires Paris-Est, Hôpital de la Salpêtrière AP-HP, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biologie des Jonctions Neuromusculaires Normales et Pathologiques ( U686 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de neurobiologie cellulaire et moléculaire ( NBCM ), Centre National de la Recherche Scientifique ( CNRS ), Institut de Neurobiologie Alfred Fessard ( INAF ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Refractory Period, Electrophysiological, MESH: Muscle Contraction, MESH : Muscle Weakness, medicine.disease_cause, Synaptic Transmission, MESH: Motor Endplate, Mice, MESH : Locomotion, 0302 clinical medicine, Missense mutation, MESH : Female, Receptors, Cholinergic, MESH: Animals, Genetics (clinical), MESH : Synaptic Transmission, 0303 health sciences, Mutation, Muscle Weakness, MESH: Muscle Weakness, General Medicine, Congenital myasthenic syndrome, Null allele, medicine.anatomical_structure, Female, MESH: Receptor Protein-Tyrosine Kinases, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, MESH: Refractory Period, Electrophysiological, Locomotion, Muscle Contraction, Muscle contraction, medicine.medical_specialty, MESH: Axons, MESH: Myasthenic Syndromes, Congenital, MESH : Male, Diaphragm, MESH : Axons, Mutation, Missense, Neuromuscular Junction, MESH: Locomotion, MESH: Microscopy, Electron, Biology, MESH : Myasthenic Syndromes, Congenital, Motor Endplate, Neuromuscular junction, 03 medical and health sciences, Internal medicine, MESH : Mice, Genetics, medicine, MESH: Synaptic Transmission, Animals, Humans, Kyphosis, Molecular Biology, MESH: Mice, 030304 developmental biology, Myasthenic Syndromes, Congenital, MESH: Mutation, Missense, MESH : Kyphosis, MESH: Receptors, Cholinergic, MESH: Humans, MESH : Humans, MESH : Motor Endplate, Receptor Protein-Tyrosine Kinases, Muscle weakness, MESH : Receptor Protein-Tyrosine Kinases, MESH : Receptors, Cholinergic, medicine.disease, MESH : Disease Models, Animal, MESH : Microscopy, Electron, Axons, Myasthenia gravis, MESH: Male, Disease Models, Animal, Microscopy, Electron, MESH : Refractory Period, Electrophysiological, Endocrinology, MESH: Diaphragm, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Muscle Contraction, MESH : Neuromuscular Junction, MESH : Animals, MESH: Neuromuscular Junction, MESH : Diaphragm, MESH: Disease Models, Animal, MESH: Kyphosis, MESH: Female, MESH : Mutation, Missense, 030217 neurology & neurosurgery
Abstract

International audience; In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic missense and a null mutation were identified in a patient suffering from a congenital myasthenic syndrome (CMS). We generated one mouse line carrying the homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second hemizygous line, resembling the patient genotype, with the V789M mutation on one allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding weight, muscle function and viability. In contrast, adult musk(V789M/-) mice suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or nerve-induced stimulation. A profound tetanic fade is observed following nerve-evoked muscle contraction, and fatigue resistance is severely impaired upon a train of tetanic nerve stimulations. Electrophysiological measurements indicate that fatigable muscle weakness is due to impaired neurotransmission as observed in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice exhibits pronounced changes in endplate architecture, distribution and innervation pattern. Thus, the missense mutation V789M in MuSK acts as a hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-) mutants. These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations.

Published
2008
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7. SIMONE: a realistic neural network simulator to reproduce MEA-based recordings

Author

Isabelle E. Magnin, Christophe Pouzat, Blaise Yvert, Antoine Chaffiol, R. Escola, Régis Guillemaud, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de physiologie cérébrale (LPC - UMR 8118), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Electronique et des Technologies de l'Information ( CEA-LETI ), Université Grenoble Alpes [Saint Martin d'Hères]-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de physiologie cérébrale ( LPC - UMR 8118 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
MESH: Microelectrodes, Computer science, MESH: Neurons, Action Potentials, Synaptic Transmission, American cockroach, law.invention, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Application-specific integrated circuit, Relay, law, SpikeOMatic, Preprocessor, SIMONE, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH : Algorithms, MESH: Action Potentials, Neurons, 0303 health sciences, MESH : Synaptic Transmission, Artificial neural network, General Neuroscience, Rehabilitation, simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH : Computer Simulation, Spike sorting, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Probability distribution, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Algorithm, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithms, Data compression, noise, Models, Neurological, Biomedical Engineering, extracellular, MESH: Algorithms, spike sorting, MESH : Neurons, 03 medical and health sciences, MESH: Computer Simulation, Robustness (computer science), MESH : Action Potentials, MESH: Models, Neurological, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], spike detection, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Internal Medicine, Electronic engineering, MESH: Synaptic Transmission, MESH : Models, Neurological, Computer Simulation, integrate-and-fire, 030304 developmental biology, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, MESH: Nerve Net, MESH : Microelectrodes, MESH : Nerve Net, Nerve Net, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], multielectrode array (MEA), Microelectrodes, 030217 neurology & neurosurgery
Abstract

International audience; Contemporary multielectrode arrays (MEAs) used to record extracellular activity from neural tissues can deliver data at rates on the order of 100 Mbps. Such rates require efficient data compression and/or preprocessing algorithms implemented on an application specific integrated circuit (ASIC) close to the MEA. We present SIMONE (Statistical sIMulation Of Neuronal networks Engine), a versatile simulation tool whose parameters can be either fixed or defined by a probability distribution. We validated our tool by simulating data recorded from the first olfactory relay of an insect. Different key aspects make this tool suitable for testing the robustness and accuracy of neural signal processing algorithms (such as the detection, alignment, and classification of spikes). For instance, most of the parameters can be defined by a probabilistic distribution, then tens of simulations may be obtained from the same scenario. This is especially useful when validating the robustness of the processing algorithm. Moreover, the number of active cells and the exact firing activity of each one of them is perfectly known, which provides an easy way to test accuracy.

Published
2008
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8. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse

Author

Philippe Rostaing, Christine Petit, M'hamed Grati, Ghislaine Hamard, Régis Nouvian, Saaid Safieddine, Marie-Christine Simmler, Amel Bahloul, Antoine Triller, Isabelle Roux, Isabelle Perfettini, Paul Avan, Morgane Le Gall, Tobias Moser, Génétique des Déficits Sensoriels, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Otolaryngology and Center for Molecular Physiology of the Brain, Georg-August-University = Georg-August-Universität Göttingen, The Wellcome Trust Sanger Institute [Cambridge], Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] (PRHTEC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie cellulaire de la synapse normale et pathologique, Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Biophysique Neurosensorielle [Neuro-Dol], Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Foundation Louis-Jeantet and the French Ministry of Research (ACI 'Biologie du Développement et Physiologie intégrative') , the European Commission FP6 Integrated Project EuroHear LSHG-CT-2004-512063, Human Frontiers Science Program, the Deutsche Forschungsgemeinschaft, (Center for Molecular Physiology of the Brain), MENRT, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Georg-August-Universität Göttingen, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] ( PRHTEC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuro-Dol ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Neuro-Dol - Clermont Auvergne ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Université Clermont Auvergne ( UCA ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Georg-August-University [Göttingen], École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Chaire Génétique et physiologie cellulaire, Laboratoire d'Electronique et Systèmes de Télécommunications (LEST), Université de Brest (UBO)-Ecole Nationale Supérieure des Télécommunications de Bretagne-Centre National de la Recherche Scientifique (CNRS), Université de Brest (UBO), This work was supported by grants from the FoundationLouis-Jeantet and the French Ministry of Research (ACI ‘‘Biologie duDeveloppement et Physiologie integrative’’) to C.P., Human Frontiers Science Program to T.M. and S.S., and the Deutsche Forschungsgemeinschaft to T.M. (Centerfor Molecular Physiology of the Brain)., École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Neuro-Dol - Clermont Auvergne (Neuro-Dol), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA)

Subjects
Auditory Pathways, Time Factors, [SDV]Life Sciences [q-bio], MESH: Synaptosomal-Associated Protein 25, Synaptogenesis, Syntaxin 1, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Ribbon synapse, Deafness, MESH : Synaptosomal-Associated Protein 25, Membrane Fusion, Synaptic Transmission, MESH: Mice, Knockout, MESH: Synapses, Mice, 0302 clinical medicine, MESH: Syntaxin 1, MESH: Cochlea, OTOF, MESH: Animals, Mice, Knockout, 0303 health sciences, MESH : Synaptic Transmission, MESH: Exocytosis, MESH : Hair Cells, Inner, MESH : Evoked Potentials, Auditory, Brain Stem, SNAP25, Anatomy, Cell biology, Cochlea, Synaptic vesicle exocytosis, medicine.anatomical_structure, MESH: Auditory Pathways, MESH: Calcium, MESH : Synaptic Vesicles, Hair cell, Synaptic Vesicles, MESH: Membrane Proteins, MESH : Synapses, MESH : Time Factors, MESH : Cochlea, MESH : Deafness, Synaptosomal-Associated Protein 25, MESH: Deafness, MESH : Mice, Inbred C57BL, Biology, MESH: Membrane Fusion, Synaptic vesicle, General Biochemistry, Genetics and Molecular Biology, Exocytosis, MESH : Exocytosis, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH : Membrane Fusion, MESH : Mice, medicine, Evoked Potentials, Auditory, Brain Stem, MESH: Synaptic Transmission, Animals, Humans, MESH : Calcium, MESH: Mice, 030304 developmental biology, Hair Cells, Auditory, Inner, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH : Humans, MESH: Time Factors, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Membrane Proteins, MESH : Syntaxin 1, MESH: Synaptic Vesicles, MESH: Hair Cells, Inner, Mice, Inbred C57BL, MESH : Membrane Proteins, Synapses, MESH : Mice, Knockout, MESH: Evoked Potentials, Auditory, Brain Stem, Calcium, MESH : Animals, MESH : Auditory Pathways, sense organs, 030217 neurology & neurosurgery
Abstract

International audience; The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synaptogenesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse.

Published
2006
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9. Optimal information storage and the distribution of synaptic weights: perceptron versus Purkinje cell

Author

Brunel, Nicolas, Hakim, Vincent, Isope, Philippe, Nadal, Jean-Pierre, Barbour, Boris, Neurophysique et physiologie du système moteur (NPSM), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurobiologie (UMR 8544) (NEURO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurophysique et physiologie du système moteur ( NPSM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique Statistique de l'ENS ( LPS ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurobiologie (UMR 8544) ( NEURO ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Rats, [ PHYS.COND.CM-DS-NN ] Physics [physics]/Condensed Matter [cond-mat]/Disordered Systems and Neural Networks [cond-mat.dis-nn], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Models, Neurological, Synaptic Transmission, MESH: Synapses, MESH : Learning, Purkinje Cells, MESH: Afferent Pathways, MESH: Neural Networks (Computer), MESH: Purkinje Cells, MESH: Models, Neurological, MESH: Synaptic Transmission, Animals, Learning, MESH : Models, Neurological, MESH: Animals, [PHYS.COND.CM-DS-NN]Physics [physics]/Condensed Matter [cond-mat]/Disordered Systems and Neural Networks [cond-mat.dis-nn], MESH: Excitatory Postsynaptic Potentials, Afferent Pathways, MESH : Synaptic Transmission, MESH : Afferent Pathways, MESH : Neural Networks (Computer), MESH : Rats, MESH : Reproducibility of Results, MESH : Excitatory Postsynaptic Potentials, MESH : Purkinje Cells, Excitatory Postsynaptic Potentials, Reproducibility of Results, Neural Inhibition, MESH: Neural Inhibition, Rats, MESH: Reproducibility of Results, MESH: Nerve Net, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Synapses, MESH : Nerve Net, MESH: Learning, Neural Networks, Computer, MESH : Animals, Nerve Net, MESH : Synapses, MESH : Neural Inhibition
Abstract

International audience; It is widely believed that synaptic modifications underlie learning and memory. However, few studies have examined what can be deduced about the learning process from the distribution of synaptic weights. We analyze the perceptron, a prototypical feedforward neural network, and obtain the optimal synaptic weight distribution for a perceptron with excitatory synapses. It contains more than 50% silent synapses, and this fraction increases with storage reliability: silent synapses are therefore a necessary byproduct of optimizing learning and reliability. Exploiting the classical analogy between the perceptron and the cerebellar Purkinje cell, we fitted the optimal weight distribution to that measured for granule cell-Purkinje cell synapses. The two distributions agreed well, suggesting that the Purkinje cell can learn up to 5 kilobytes of information, in the form of 40,000 input-output associations.

Published
2004
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10. Electrical synapses and synchrony: the role of intrinsic currents

Author

David Golomb, David Hansel, Benjamin Pfeuty, Germán Mato, Centre de neurophysique, physiologie, pathologie (UMR 8119), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Departamento de Fisica Teorica, Universidad Autonoma de Madrid (UAM), Centro Atómico Bariloche [Argentine], Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Comisión Nacional de Energía Atómica [ARGENTINA] (CNEA), Department of Physiology and Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev (BGU), Laboratoire Franco-Israelien de Neurophysiologie et Neurophysique des Systèmes, Université Paris Descartes - Paris 5 (UPD5), Centre de neurophysique, physiologie, pathologie ( UMR 8119 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad Autonoma de Madrid ( UAM ), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] ( CONICET ) -Comisión Nacional de Energía Atómica [ARGENTINA] ( CNEA ), Ben-Gurion University of the Negev ( BGU ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Lamotte D'Incamps, Boris

Subjects
Time Factors, Neural Conduction, MESH: Neurons, Neocortex, Synaptic Transmission, Synchronization, MESH: Synapses, MESH: Neocortex, 0302 clinical medicine, MESH: Neural Conduction, Premovement neuronal activity, MESH: Sodium, MESH : Mathematics, Neurons, Physics, MESH : Synaptic Transmission, 0303 health sciences, MESH : Neural Networks (Computer), General Neuroscience, MESH : Computer Simulation, Electrical Synapses, medicine.anatomical_structure, MESH : Sodium, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Synapses, MESH : Time Factors, Models, Neurological, Behavioral/Systems/Cognitive, MESH : Neural Conduction, Stability (probability), MESH : Neurons, 03 medical and health sciences, MESH: Neural Networks (Computer), MESH: Computer Simulation, MESH: Models, Neurological, medicine, MESH: Synaptic Transmission, MESH : Models, Neurological, Computer Simulation, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Neocortex, 030304 developmental biology, Quantitative Biology::Neurons and Cognition, Sodium, MESH: Time Factors, Skew, MESH: Mathematics, Conductance, MESH : Potassium, nervous system, Asynchronous communication, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Synapses, MESH: Potassium, Potassium, Neural Networks, Computer, Neuroscience, Mathematics, 030217 neurology & neurosurgery
Abstract

Electrical synapses are ubiquitous in the mammalian CNS. Particularly in the neocortex, electrical synapses have been shown to connect low-threshold spiking (LTS) as well as fast spiking (FS) interneurons. Experiments have highlighted the roles of electrical synapses in the dynamics of neuronal networks. Here we investigate theoretically how intrinsic cell properties affect the synchronization of neurons interacting by electrical synapses. Numerical simulations of a network of conductance-based neurons randomly connected with electrical synapses show that potassium currents promote synchrony, whereas the persistent sodium current impedes it. Furthermore, synchrony varies with the firing rate in qualitatively different ways depending on the intrinsic currents. We also study analytically a network of quadratic integrate-and-fire neurons. We relate the stability of the asynchronous state of this network to the phase-response function (PRF), which characterizes the effect of small perturbations on the firing timing of the neurons. In particular, we show that the greater the skew of the PRF toward the first half of the period, the more stable the asynchronous state. Combining our simulations with our analytical results, we establish general rules to predict the dynamic state of large networks of neurons coupled with electrical synapses. Our work provides a natural explanation for surprising experimental observations that blocking electrical synapses may increase the synchrony of neuronal activity. It also suggests different synchronization properties for LTS and FS cells. Finally, we propose to further test our predictions in experiments using dynamic clamp techniques.

Published
2003

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