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  • 1
    Publication Date: 2014-08-03
    Description: Article Tuberous sclerosis complex (TSC) is a rare genetic condition characterized by epileptic seizures that start in infancy. Here, the authors show that these seizures are modulated by GluN2C-containing NMDA receptors in the cortex of a mouse model of TSC, and that suppressing their activity attenuates seizures. Nature Communications doi: 10.1038/ncomms5563 Authors: N. Lozovaya, S. Gataullina, T. Tsintsadze, V. Tsintsadze, E. Pallesi-Pocachard, M. Minlebaev, N. A. Goriounova, E. Buhler, F. Watrin, S. Shityakov, A. J. Becker, A. Bordey, M. Milh, D. Scavarda, C. Bulteau, G. Dorfmuller, O. Delalande, A. Represa, C. Cardoso, O. Dulac, Y. Ben-Ari, N. Burnashev
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 2
    Publication Date: 1999-06-12
    Description: Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zamanillo, D -- Sprengel, R -- Hvalby, O -- Jensen, V -- Burnashev, N -- Rozov, A -- Kaiser, K M -- Koster, H J -- Borchardt, T -- Worley, P -- Lubke, J -- Frotscher, M -- Kelly, P H -- Sommer, B -- Andersen, P -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1805-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Neuroscience, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364547" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Bicuculline/pharmacology ; Calcium/metabolism ; Dendrites/physiology/ultrastructure ; GABA Antagonists/pharmacology ; Gene Expression ; Gene Targeting ; Genes, Immediate-Early ; Glutamic Acid/pharmacology/physiology ; Hippocampus/cytology/physiology ; Long-Term Potentiation/*physiology ; *Maze Learning ; Mice ; Mice, Inbred C57BL ; Pyramidal Cells/*physiology/ultrastructure ; Receptors, AMPA/genetics/*physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Synapses/*physiology/ultrastructure ; Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2001-06-30
    Description: Plasticity of mature hippocampal CA1 synapses is dependent on l-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors containing the glutamate receptor A (GluR-A) subunit. In GluR-A-deficient mice, plasticity could be restored by controlled expression of green fluorescent protein (GFP)-tagged GluR-A, which contributes to channel formation and displayed the developmental redistribution of AMPA receptors in CA1 pyramidal neurons. Long-term potentiation (LTP) induced by pairing or tetanic stimulation was rescued in adult GluR-A(-/-) mice when (GFP)GluR-A expression was constitutive or induced in already fully developed pyramidal cells. This shows that GluR-A-independent forms of synaptic plasticity can mediate the establishment of mature hippocampal circuits that are prebuilt to express GluR-A-dependent LTP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mack, V -- Burnashev, N -- Kaiser, K M -- Rozov, A -- Jensen, V -- Hvalby, O -- Seeburg, P H -- Sakmann, B -- Sprengel, R -- New York, N.Y. -- Science. 2001 Jun 29;292(5526):2501-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11431570" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Dendrites/metabolism ; Doxycycline/pharmacology ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Green Fluorescent Proteins ; Hippocampus/metabolism/*physiology ; *Long-Term Potentiation ; Luminescent Proteins ; Mice ; Mice, Transgenic ; Neuronal Plasticity ; Patch-Clamp Techniques ; Pyramidal Cells/metabolism/*physiology ; Receptors, AMPA/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Synapses/metabolism/*physiology ; Transgenes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1992-06-12
    Description: Glutamate-operated ion channels (GluR channels) of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate subtype are found in both neurons and glial cells of the central nervous system. These channels are assembled from the GluR-A, -B, -C, and -D subunits; channels containing a GluR-B subunit show an outwardly rectifying current-voltage relation and low calcium permeability, whereas channels lacking the GluR-B subunit are characterized by a doubly rectifying current-voltage relation and high calcium permeability. Most cell types in the central nervous system coexpress several subunits, including GluR-B. However, Bergmann glia in rat cerebellum do not express GluR-B subunit genes. In a subset of cultured cerebellar glial cells, likely derived from Bergmann glial cells. GluR channels exhibit doubly rectifying current-voltage relations and high calcium permeability, whereas GluR channels of cerebellar neurons have low calcium permeability. Thus, differential expression of the GluR-B subunit gene in neurons and glia is one mechanism by which functional properties of native GluR channels are regulated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burnashev, N -- Khodorova, A -- Jonas, P -- Helm, P J -- Wisden, W -- Monyer, H -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1992 Jun 12;256(5063):1566-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Cell Membrane Permeability ; Cells, Cultured ; Cerebellum/*physiology ; Gene Expression ; Glutamates/physiology ; In Vitro Techniques ; Ion Channel Gating ; Neuroglia/*physiology ; Nucleic Acid Hybridization ; RNA, Messenger/genetics ; Rats ; Receptors, Kainic Acid ; Receptors, Neurotransmitter/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1992-09-04
    Description: The N-methyl-D-aspartate (NMDA) receptor forms a cation-selective channel with a high calcium permeability and sensitivity to channel block by extracellular magnesium. These properties, which are believed to be important for the induction of long-term changes in synaptic strength, are imparted by asparagine residues in a putative channel-forming segment of the protein, transmembrane 2 (TM2). In the NR1 subunit, replacement of this asparagine by a glutamine residue decreases calcium permeability of the channel and slightly reduces magnesium block. The same substitution in NR2 subunits strongly reduces magnesium block and increases the magnesium permeability but barely affects calcium permeability. These asparagines are in a position homologous to the site in the TM2 region (Q/R site) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that is occupied by either glutamine (Q) or arginine (R) and that controls divalent cation permeability of the AMPA receptor channel. Hence AMPA and NMDA receptor channels contain common structural motifs in their TM2 segments that are responsible for some of their ion selectivity and conductance properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burnashev, N -- Schoepfer, R -- Monyer, H -- Ruppersberg, J P -- Gunther, W -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1415-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abteilung Zellphysiologie, Max-Planck-Institut fur Medizinische Forschung, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Asparagine/*chemistry ; Binding Sites ; Calcium/*metabolism/pharmacology ; Cell Line ; Electric Conductivity ; Glutamates/pharmacology ; Glutamic Acid ; Ion Channels/chemistry/*physiology ; Magnesium/metabolism/*pharmacology ; Mice ; Molecular Sequence Data ; Mutagenesis ; Oocytes/metabolism ; Permeability ; Rats ; Receptors, N-Methyl-D-Aspartate/chemistry/genetics/*physiology ; Structure-Activity Relationship ; Transfection ; Xenopus
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 1990-09-28
    Description: In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sommer, B -- Keinanen, K -- Verdoorn, T A -- Wisden, W -- Burnashev, N -- Herb, A -- Kohler, M -- Takagi, T -- Sakmann, B -- Seeburg, P H -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1580-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neuroendocrinology, Center for Molecular Biology, University of Heidelberg, F.R.G.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1699275" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain/*metabolism ; DNA/genetics ; Exons ; Genomic Library ; Glutamates/*metabolism/pharmacology ; Ibotenic Acid/*analogs & derivatives/metabolism/pharmacology ; Ion Channels/*physiology ; Kinetics ; Molecular Sequence Data ; Oligonucleotide Probes ; Organ Specificity ; *RNA Splicing ; RNA, Messenger/*genetics ; Rats ; Receptors, AMPA ; Receptors, Glutamate ; Receptors, Neurotransmitter/drug effects/*genetics/physiology ; Recombinant Proteins/metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 1991-06-21
    Description: Functional glutamate receptor (GluRs) were transiently expressed in cultured mammalian cells from cloned complementary DNAs encoding GluR-A, -B, -C, or -D polypeptides. The steady-state current-voltage (I-V) relations of glutamate- and kainate-induced currents through homomeric channels fell into two classes: channels composed of either the GluR-A, -C, and -D subunits showed doubly rectifying I-V curves, and channels composed of the GluR-B subunits displayed simple outward rectification. The presence of GluR-B subunits in heteromeric GluRs determined the I-V behavior of the resulting channels. Site-directed mutagenesis identified a single amino acid difference (glutamine to arginine) in the putative transmembrane segment TM2 responsible for subunit-specific I-V relationships. The properties of heteromeric wild-type and mutant GluRs revealed that the dominance of GluR-B is due to the arginine residue in the TM2 region.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Verdoorn, T A -- Burnashev, N -- Monyer, H -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1991 Jun 21;252(5013):1715-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1710829" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; DNA Mutational Analysis ; Glutamates/physiology ; Humans ; Ion Channel Gating ; Ion Channels/*physiology ; Macromolecular Substances ; Membrane Glycoproteins/physiology ; Molecular Sequence Data ; Oligonucleotides/chemistry ; Receptors, Glutamate ; Receptors, Neurotransmitter/*physiology ; Recombinant Proteins ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-02-08
    Description: We report that the oxytocin-mediated neuroprotective gamma-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naive mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tyzio, Roman -- Nardou, Romain -- Ferrari, Diana C -- Tsintsadze, Timur -- Shahrokhi, Amene -- Eftekhari, Sanaz -- Khalilov, Ilgam -- Tsintsadze, Vera -- Brouchoud, Corinne -- Chazal, Genevieve -- Lemonnier, Eric -- Lozovaya, Natalia -- Burnashev, Nail -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):675-9. doi: 10.1126/science.1247190.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503856" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics/metabolism ; Behavior, Animal ; Bumetanide/administration & dosage ; Chlorides/metabolism ; *Cytoprotection ; Disease Models, Animal ; Female ; Fragile X Mental Retardation Protein/genetics ; Maternal-Fetal Exchange ; Mice ; Oxytocin/*metabolism ; Parturition ; Pregnancy ; Rats ; Valproic Acid/pharmacology ; gamma-Aminobutyric Acid/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 1992-05-22
    Description: The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine. Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1). Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate- and NMDA-activated currents only when they were in heteromeric configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monyer, H -- Sprengel, R -- Schoepfer, R -- Herb, A -- Higuchi, M -- Lomeli, H -- Burnashev, N -- Sakmann, B -- Seeburg, P H -- New York, N.Y. -- Science. 1992 May 22;256(5060):1217-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology, University of Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1350383" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain/*physiology ; Cell Line ; Cloning, Molecular ; DNA/genetics ; Glutamates/pharmacology ; Glutamic Acid ; Glycine/pharmacology ; Macromolecular Substances ; Magnesium/pharmacology ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Multigene Family ; N-Methylaspartate/pharmacology ; Oligonucleotide Probes ; Organ Specificity ; Peptides ; RNA, Messenger/genetics/metabolism ; Rats ; Receptors, N-Methyl-D-Aspartate/*genetics/*metabolism ; Recombinant Proteins/drug effects/metabolism ; Sequence Homology, Nucleic Acid ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2014-10-11
    Description: Bambini-Junior et al. questioned whether our treatment in two rodent models of autism has a long-lasting effect into adulthood. In response, we show that bumetanide treatment around delivery attenuates autistic behavioral features in adult offspring. Therefore, the polarity of gamma-aminobutyric acid (GABA) actions during delivery exerts long-lasting priming actions after birth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eftekhari, Sanaz -- Shahrokhi, Amene -- Tsintsadze, Vera -- Nardou, Romain -- Brouchoud, Corinne -- Conesa, Magali -- Burnashev, Nail -- Ferrari, Diana C -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):176. doi: 10.1126/science.1256009.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. On leave from Iran University of Medical Sciences, Tehran, Iran. ; Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. On leave from Tehran University of Medical Sciences, Tehran, Iran. ; Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. ; Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. ; Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. yehezkel.ben-ari@inserm.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301611" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics ; *Cytoprotection ; Female ; Oxytocin/*metabolism ; Pregnancy ; gamma-Aminobutyric Acid/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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