n methyl d aspartate receptors

Summary

Summary: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.

Top Publications

  1. ncbi A synaptic model of memory: long-term potentiation in the hippocampus
    T V Bliss
    Division of Neurophysiology and Neuropharmacology, National Institute of Medical Research, Mill Hill, London, UK
    Nature 361:31-9. 1993
  2. ncbi Developmental and regional expression in the rat brain and functional properties of four NMDA receptors
    H Monyer
    Laboratory of Molecular Neuroscience, Heidelberg University, Federal Republic of Germany
    Neuron 12:529-40. 1994
  3. pmc Structural basis of long-term potentiation in single dendritic spines
    Masanori Matsuzaki
    Department of Cell Physiology, National Institute for Physiological Sciences and The Graduate University of Advanced Studies Sokendai, Myodaiji, Okazaki 444 8787, Japan
    Nature 429:761-6. 2004
  4. ncbi Glutamate exocytosis from astrocytes controls synaptic strength
    Pascal Jourdain
    Department of Cell Biology and Morphology, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland
    Nat Neurosci 10:331-9. 2007
  5. ncbi NMDA receptor subunits: function and pharmacology
    Pierre Paoletti
    Laboratoire de Neurobiologie, CNRS UMR 8544 Ecole Normale Supérieure 46 rue d Ulm, 75005 Paris, France
    Curr Opin Pharmacol 7:39-47. 2007
  6. ncbi NMDA receptor subunits: diversity, development and disease
    S Cull-Candy
    Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK
    Curr Opin Neurobiol 11:327-35. 2001
  7. ncbi Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia
    Chang Gyu Hahn
    Cellular and Molecular Neuropathology Program, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Med 12:824-8. 2006
  8. pmc Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia
    John E Lisman
    Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Trends Neurosci 31:234-42. 2008
  9. ncbi NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo
    Yitao Liu
    Brain Research Centre, Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5
    J Neurosci 27:2846-57. 2007
  10. ncbi Hippocampal CA3 NMDA receptors are crucial for memory acquisition of one-time experience
    Kazu Nakazawa
    Howard Hughes Medical Institute, 77 Massachusetts Avenue, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Neuron 38:305-15. 2003

Research Grants

Detail Information

Publications371 found, 100 shown here

  1. ncbi A synaptic model of memory: long-term potentiation in the hippocampus
    T V Bliss
    Division of Neurophysiology and Neuropharmacology, National Institute of Medical Research, Mill Hill, London, UK
    Nature 361:31-9. 1993
    ....
  2. ncbi Developmental and regional expression in the rat brain and functional properties of four NMDA receptors
    H Monyer
    Laboratory of Molecular Neuroscience, Heidelberg University, Federal Republic of Germany
    Neuron 12:529-40. 1994
    ..Thus, the distinct expression profiles and functional properties of NR2 subunits provide a basis for NMDA channel heterogeneity in the brain...
  3. pmc Structural basis of long-term potentiation in single dendritic spines
    Masanori Matsuzaki
    Department of Cell Physiology, National Institute for Physiological Sciences and The Graduate University of Advanced Studies Sokendai, Myodaiji, Okazaki 444 8787, Japan
    Nature 429:761-6. 2004
    ..They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory...
  4. ncbi Glutamate exocytosis from astrocytes controls synaptic strength
    Pascal Jourdain
    Department of Cell Biology and Morphology, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland
    Nat Neurosci 10:331-9. 2007
    ..Thus, we provide the first combined functional and ultrastructural evidence for a physiological control of synaptic activity via exocytosis of glutamate from astrocytes...
  5. ncbi NMDA receptor subunits: function and pharmacology
    Pierre Paoletti
    Laboratoire de Neurobiologie, CNRS UMR 8544 Ecole Normale Supérieure 46 rue d Ulm, 75005 Paris, France
    Curr Opin Pharmacol 7:39-47. 2007
    ....
  6. ncbi NMDA receptor subunits: diversity, development and disease
    S Cull-Candy
    Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK
    Curr Opin Neurobiol 11:327-35. 2001
    ..Recent studies are beginning to address the functional significance of NMDAR diversity under normal and pathological conditions...
  7. ncbi Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia
    Chang Gyu Hahn
    Cellular and Molecular Neuropathology Program, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Med 12:824-8. 2006
    ..Therefore, these findings suggest that enhanced NRG1 signaling may contribute to NMDA hypofunction in schizophrenia...
  8. pmc Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia
    John E Lisman
    Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Trends Neurosci 31:234-42. 2008
    ..iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia...
  9. ncbi NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo
    Yitao Liu
    Brain Research Centre, Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5
    J Neurosci 27:2846-57. 2007
    ....
  10. ncbi Hippocampal CA3 NMDA receptors are crucial for memory acquisition of one-time experience
    Kazu Nakazawa
    Howard Hughes Medical Institute, 77 Massachusetts Avenue, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Neuron 38:305-15. 2003
    ..These results suggest that CA3 NRs play a crucial role in rapid hippocampal encoding of novel information for fast learning of one-time experience...
  11. pmc Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites
    Jun Noguchi
    Department of Cell Physiology, National Institute for Physiological Sciences and Graduate University of Advanced Studies SOKENDAI, Myodaiji, Okazaki 444 8787, Japan
    Neuron 46:609-22. 2005
    ..Spine-neck geometry is thus an important determinant of spine Ca2+ signaling, allowing small spines to be the preferential sites for isolated induction of long-term potentiation...
  12. ncbi Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways
    G E Hardingham
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Nat Neurosci 5:405-14. 2002
    ..Specific blockade of extrasynaptic NMDA receptors may effectively prevent neuron loss following stroke and other neuropathological conditions associated with glutamate toxicity...
  13. ncbi NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII
    Andres Barria
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Neuron 48:289-301. 2005
    ..The switch from NR2B to NR2A content in synaptic NMDA-Rs normally observed in many brain regions may contribute to reduced plasticity by controlling the binding of active CaMKII...
  14. pmc Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity
    Koji Yashiro
    Department of Cell and Molecular Physiology, Neuroscience Center, and Neurobiology Curriculum, University of North Carolina, Neuroscience Research Building, Campus Box 7545, 115 Mason Farm Road, Chapel Hill, NC 27599 7545, USA
    Neuropharmacology 55:1081-94. 2008
    ..Finally, we use the visual cortex as a model system to illustrate how activity-dependent modifications in the NR2A/NR2B ratio may contribute to the development of cortical functions...
  15. ncbi Mice with reduced NMDA receptor expression display behaviors related to schizophrenia
    A R Mohn
    Department of Medicine, University of North Carolina at Chapel Hill 27599 USA
    Cell 98:427-36. 1999
    ..These findings support a model in which reduced NMDA receptor activity results in schizophrenic-like behavior and reveals how pharmacological manipulation of monoaminergic pathways can affect this phenotype...
  16. ncbi Subunit arrangement and function in NMDA receptors
    Hiroyasu Furukawa
    Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, New York 10032, USA
    Nature 438:185-92. 2005
    ....
  17. ncbi Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95
    H C Kornau
    Center for Molecular Biology ZMBH, University of Heidelberg, Germany
    Science 269:1737-40. 1995
    ..The interaction of these proteins may affect the plasticity of excitatory synapses...
  18. ncbi Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons
    Daniel Saal
    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA
    Neuron 37:577-82. 2003
    ....
  19. ncbi Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain
    C Ikonomidou
    Department of Pediatric Neurology, Charite Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany
    Science 283:70-4. 1999
    ..These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors...
  20. pmc Ontogeny of postsynaptic density proteins at glutamatergic synapses
    Ronald S Petralia
    Laboratory of Neurochemistry, NIDCD NIH, 50 4142, 50 South Drive MSC 8027, Bethesda, MD 20892 8027, USA
    Mol Cell Neurosci 29:436-52. 2005
    ..Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors, and CaMKII. Other components showed more moderate changes...
  21. pmc A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain
    Shaoyu Ge
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuron 54:559-66. 2007
    ....
  22. ncbi Involvement of the CA3-CA1 synapse in the acquisition of associative learning in behaving mice
    Agnes Gruart
    Division de Neurociencias, Universidad Pablo de Olavide, 41013 Sevilla, Spain
    J Neurosci 26:1077-87. 2006
    ..Our results provide evidence of a relationship between activity-dependent synaptic plasticity and associative learning in behaving mice...
  23. ncbi Recent advances in the phencyclidine model of schizophrenia
    D C Javitt
    Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, N Y
    Am J Psychiatry 148:1301-8. 1991
    ..The purpose of the present paper is to review recent advances in the study of the molecular mechanisms of PCP action and to describe their implications for the understanding of schizophrenic pathophysiology...
  24. pmc Requirement for hippocampal CA3 NMDA receptors in associative memory recall
    Kazu Nakazawa
    Picower Center for Learning and Memory, RIKEN MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 297:211-8. 2002
    ..These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall...
  25. ncbi Subunit-specific NMDA receptor trafficking to synapses
    Andres Barria
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Neuron 35:345-53. 2002
    ..Thus, as with AMPA-Rs, synaptic trafficking of NMDA-Rs is tightly regulated and has subunit-specific rules with functionally important consequences...
  26. ncbi The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory
    J Z Tsien
    Howard Hughes Medical Institute, Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge 02139, USA
    Cell 87:1327-38. 1996
    ..Our results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories...
  27. ncbi Bidirectional synaptic plasticity regulated by phosphorylation of stargazin-like TARPs
    Susumu Tomita
    Department of Physiology, University of California at San Francisco, San Francisco, CA 94143, USA
    Neuron 45:269-77. 2005
    ..These results establish stargazin as a critical substrate in the bidirectional control of synaptic strength, which is thought to underlie aspects of learning and memory...
  28. pmc Astrocytic control of synaptic NMDA receptors
    C Justin Lee
    Center for Neural Science, Division of Life Sciences, Korea Institute of Science and Technology, Seoul, Korea
    J Physiol 581:1057-81. 2007
    ..These results suggest that astrocytic G-protein coupled receptors that increase intracellular Ca2+ can tune synaptic NMDA receptor responses...
  29. ncbi Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor
    Frank J S Lee
    Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, M5T 1R8, Ontario, Canada
    Cell 111:219-30. 2002
    ..While one interaction is involved in the inhibition of NMDA receptor-gated currents, the other is implicated in the attenuation of NMDA receptor-mediated excitotoxicity through a PI-3 kinase-dependent pathway...
  30. ncbi NMDA receptor hypofunction model of schizophrenia
    J W Olney
    Department of Psychiatry, Washington University, School of Medicine, St Louis, MO 63110 1093, USA
    J Psychiatr Res 33:523-33. 1999
    ..In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested...
  31. ncbi SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines
    Thu Jennifer Ngo-Anh
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nat Neurosci 8:642-9. 2005
    ..Thus, blocking SK channels facilitates the induction of long-term potentiation by enhancing NMDAR-dependent Ca(2+) signals within dendritic spines...
  32. ncbi Neuronal activity regulates diffusion across the neck of dendritic spines
    Brenda L Bloodgood
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    Science 310:866-9. 2005
    ..The regulation of diffusional coupling provides a possible mechanism for determining the amplitude of postsynaptic potentials and the accumulation of plasticity-inducing molecules within the spine head...
  33. ncbi Internalization of ionotropic glutamate receptors in response to mGluR activation
    E M Snyder
    Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA
    Nat Neurosci 4:1079-85. 2001
    ..These data suggest that expression of mGluR-LTD is at least partly postsynaptic, and that a functional consequence of dendritic protein synthesis is the regulation of glutamate receptor trafficking...
  34. pmc Communication between the synapse and the nucleus in neuronal development, plasticity, and disease
    Sonia Cohen
    F M Kirby Neurobiology Center, Children s Hospital Boston and Departments of Neurology and Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Cell Dev Biol 24:183-209. 2008
    ....
  35. ncbi Regulation of NMDA receptor trafficking by amyloid-beta
    Eric M Snyder
    Laboratory for Molecular and Cellular Neuroscience, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Neurosci 8:1051-8. 2005
    ..Dephosphorylation of the NMDA receptor subunit NR2B at Tyr1472 correlated with receptor endocytosis. These data indicate a new mechanism by which amyloid-beta can cause synaptic dysfunction and contribute to Alzheimer disease pathology...
  36. ncbi Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia
    Kenji Hashimoto
    Department of Psychiatry, Graduate School of Medicine, Chiba University, Japan
    Arch Gen Psychiatry 60:572-6. 2003
    ..The aim of this study was to examine whether serum levels of D- and L-serine in patients with schizophrenia are different from those of healthy controls...
  37. ncbi Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A
    S Das
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 393:377-81. 1998
    ..These data suggest that NR3A is involved in the development of synaptic elements by modulating NMDAR activity...
  38. ncbi Genetic enhancement of learning and memory in mice
    Y P Tang
    Department of Molecular Biology, Princeton University, New Jersey 08544 1014, USA
    Nature 401:63-9. 1999
    ..Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible...
  39. ncbi The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments
    Robert W Buchanan
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Am J Psychiatry 164:1593-602. 2007
    ..Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments...
  40. ncbi Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia
    D Umbricht
    Psychiatric University Hospital, Department of Research, PO Box 68, Zurich 8029, Switzerland
    Arch Gen Psychiatry 57:1139-47. 2000
    ....
  41. pmc Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma
    Josep Dalmau
    Department of Neurology, Division of Neuro Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Ann Neurol 61:25-36. 2007
    ..To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis...
  42. pmc Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
    Josep Dalmau
    Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lancet Neurol 7:1091-8. 2008
    ..We aimed to analyse the clinical and immunological features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures...
  43. ncbi Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo
    Yugo Fukazawa
    Mitsubishi Kagaku Institute of Life Sciences MITILS, Machida, 194 8511, Tokyo, Japan
    Neuron 38:447-60. 2003
    ..These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP...
  44. ncbi Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus
    Thomas E Bartlett
    MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
    Neuropharmacology 52:60-70. 2007
    ..4 microM. The lack of effect of 0.1 microM NVP on LTD contrasts with its marked effect on LTP and raises the possibility that different NVP-sensitive NR2 subunit-containing NMDA receptors are required for LTP and LTD in this preparation...
  45. ncbi Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice
    T Kutsuwada
    Department of Neuropharmacology, Faculty of Medicine, Niigata University, Japan
    Neuron 16:333-44. 1996
    ..In the hippocampus of the mutant mice, synaptic NMDA responses and longterm depression were abolished. These results suggest that the epsilon 2 subunit plays an essential role in both neuronal pattern formation and synaptic plasticity...
  46. ncbi Modulation of triheteromeric NMDA receptors by N-terminal domain ligands
    Christopher J Hatton
    Laboratoire de Neurobiologie, CNRS UMR 8544, Ecole Normale Supérueure, Paris, France
    Neuron 46:261-74. 2005
    ..Similarly, NR1/2A/2C receptors are inhibited by zinc with high potency but low efficacy. Therefore, interactions between homologous N-terminal domains determine the unique pharmacological properties of triheteromeric NMDARs...
  47. ncbi The Yin and Yang of NMDA receptor signalling
    Giles E Hardingham
    Department of Preclinical Veterinary Sciences, Royal School of Veterinary Studies, Edinburgh University, Summerhall, UK
    Trends Neurosci 26:81-9. 2003
    ....
  48. ncbi Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor
    T Nakazawa
    Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    J Biol Chem 276:693-9. 2001
    ..These data suggest that Tyr-1472 phosphorylation of GluR epsilon 2 is important for synaptic plasticity...
  49. ncbi Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice
    S G Grant
    Center for Neurobiology and Behavior, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032
    Science 258:1903-10. 1992
    ..Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus...
  50. pmc An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity
    Akira Terashima
    Developmental Synaptic Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA
    Neuron 57:872-82. 2008
    ..In addition, deletion of PICK1 or blockade of PICK1 PDZ binding prevented NMDAR-dependent LTD. Thus, PICK1 plays a critical role in bidirectional NMDAR-dependent long-term synaptic plasticity in the hippocampus...
  51. ncbi SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala
    E S Louise Faber
    The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia
    Nat Neurosci 8:635-41. 2005
    ..Calcium influx through NMDARs activates SK channels and shunts the resultant excitatory postsynaptic potential. These results demonstrate a new role for SK channels as postsynaptic regulators of synaptic efficacy...
  52. ncbi NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation
    E Shimizu
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544 1014, USA
    Science 290:1170-4. 2000
    ..Such a synaptic reinforcement process may also serve as a cellular means by which the new memory is transferred from the hippocampus to the cortex for permanent storage...
  53. ncbi Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia
    Joseph T Coyle
    McLean Hospital, Belmont, Massachusetts 02478, USA
    Ann N Y Acad Sci 1003:318-27. 2003
    ..Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia...
  54. ncbi 5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition
    Yves P Auberson
    Novartis Pharma AG, Klybeckstrasse 141, 4002 Basel, Switzerland
    Bioorg Med Chem Lett 12:1099-102. 2002
    ..Their preference for the human NMDAR 1A/2A over 1A/2B subunit composition was optimized, leading to (1RS,1'S)-PEAQX (9r), which shows a >100-fold selectivity...
  55. pmc NMDA receptor surface mobility depends on NR2A-2B subunits
    Laurent Groc
    Physiologie Cellulaire de la Synapse, Unité Mixte de Recherche UMR 5091, Centre National de la Recherche Scientifique CNRS, Universite Bordeaux 2, 33077 Bordeaux, France
    Proc Natl Acad Sci U S A 103:18769-74. 2006
    ..This suggests that the switch in synaptic NMDAR subtypes depends on the regulation of the receptor surface trafficking...
  56. ncbi LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1
    D R Grosshans
    Department of Pharmacology, University of Colorado Health Science Center, 4200 E Ninth Ave Box C236, Denver, Colorado 80262, USA
    Nat Neurosci 5:27-33. 2002
    ..The present study suggests a developmental shift in the LTP-dependent trafficking of AMPA receptors. Moreover, our results indicate that insertion of NMDA receptors may be a key step in regulating synaptic plasticity...
  57. ncbi Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking
    Penelope J Hallett
    MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurosci 26:4690-700. 2006
    ..Modification of these pathways may be a useful therapeutic target for Parkinson's disease and other basal ganglia disorders in which abnormal function of striatal NMDA receptors contributes to the symptoms of the diseases...
  58. ncbi NMDA receptors are critical for unleashing consolidated auditory fear memories
    Cyrinne Ben Mamou
    Psychology Department, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec H3A 1B1, Canada
    Nat Neurosci 9:1237-9. 2006
    ..These findings suggest that NMDA receptors in the amygdala are critical for transforming a memory from a fixed to a labile state...
  59. ncbi Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs
    H Markram
    Max Planck Institut fur medizinische Forschung, Abteilung Zellphysiologie, Jahnstrasse 29, D 69120 Heidelberg, Germany
    Science 275:213-5. 1997
    ..These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons...
  60. ncbi Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors
    Tommaso Fellin
    Istituto CNR di Neuroscienze, Universita di Padova, Viale G Colombo 3, 35121, Italy
    Neuron 43:729-43. 2004
    ..Our results reveal a distinct mechanism for neuronal excitation and synchrony and highlight a functional link between astrocytic glutamate and extrasynaptic NMDA receptors...
  61. ncbi Heteromeric NMDA receptors: molecular and functional distinction of subtypes
    H Monyer
    Center for Molecular Biology, University of Heidelberg, Germany
    Science 256:1217-21. 1992
    ..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...
  62. ncbi Activation of NR2A-containing NMDA receptors is not obligatory for NMDA receptor-dependent long-term potentiation
    Carl Weitlauf
    Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Neurosci 25:8386-90. 2005
    ..Furthermore, our data demonstrate that care must be exercised in the interpretation of data generated with AAM077 when the compound is applied before an agonist...
  63. ncbi Long-term potentiation--a decade of progress?
    R C Malenka
    Nancy Friend Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA
    Science 285:1870-4. 1999
    ..This review presents a current understanding of the molecular mechanisms of this long-lasting increase in synaptic strength and describes a simple model that unifies much of the data that previously were viewed as contradictory...
  64. ncbi Synaptic distribution of the NR1, NR2A and NR2B subunits of the N-methyl-d-aspartate receptor in the rat lumbar spinal cord revealed with an antigen-unmasking technique
    Gergely G Nagy
    Spinal Cord Group, West Medical Building, Institute of Biomedical and Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK
    Eur J Neurosci 20:3301-12. 2004
    ..These results suggest that many, but not all, glutamatergic synapses in the spinal cord possess NMDA receptors and that subunit composition varies in different regions...
  65. ncbi The role of CA3 hippocampal NMDA receptors in paired associate learning
    Tarek Rajji
    Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
    J Neurosci 26:908-15. 2006
    ..The findings suggest that CA3 NMDA receptors specifically support the encoding of new experiences to involve incidental and contingent associations...
  66. ncbi D-serine augments NMDA-NR2B receptor-dependent hippocampal long-term depression and spatial reversal learning
    Steven Duffy
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    Neuropsychopharmacology 33:1004-18. 2008
    ..By enhancing this form of synaptic plasticity, D-serine could improve cognitive flexibility in psychiatric disorders characterized by perseveration of aberrant ideation or behaviors...
  67. ncbi Synaptic and extrasynaptic NMDA receptor NR2 subunits in cultured hippocampal neurons
    Christopher G Thomas
    Vollum Inst, OHSU L474, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Neurophysiol 95:1727-34. 2006
    ..Truncation of the NR2A C terminus did not eliminate synaptic expression of NR2A-containing receptors. Our results indicate that NR2A- and NR2B-containing receptors can be located in either synaptic or extrasynaptic compartments...
  68. pmc Regulation of NMDA receptors by phosphorylation
    Bo Shiun Chen
    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Neuropharmacology 53:362-8. 2007
    ..Here we summarize recent advances in the characterization of NMDA receptor phosphorylation, emphasizing subunit-specific phosphorylation, which differentially controls the trafficking and surface expression of NMDA receptors...
  69. ncbi N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease
    Mannie M Y Fan
    Department of Psychiatry Kinsmen Laboratories of Neurological Research, Brain Research Centre, University of British Columbia, Vancouver, BC, Canada
    Prog Neurobiol 81:272-93. 2007
    ..Here, we review the literature to date and recent findings concerning the role of NMDARs in HD pathogenesis...
  70. ncbi The drugs don't work-or do they? Pharmacological and transgenic studies of the contribution of NMDA and GluR-A-containing AMPA receptors to hippocampal-dependent memory
    D M Bannerman
    Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, England
    Psychopharmacology (Berl) 188:552-66. 2006
    ..The aim of this article is to provide a review of studies using N-methyl-D-aspartate (NMDA) receptor antagonists to assess the hippocampal long-term potentiation (LTP)/learning hypothesis...
  71. pmc Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter
    Christine I Nam
    Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720 3200, USA
    Proc Natl Acad Sci U S A 102:6137-42. 2005
    ..These results demonstrate that postsynaptic assembly of the glutamatergic synapse may be initiated by presynaptic beta-neurexin and that glutamate release also is required for maturation of synapses...
  72. ncbi Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain
    Hon Kit Wong
    Department of Biology and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China
    J Comp Neurol 450:303-17. 2002
    ..This information will facilitate future research on NMDARs by providing clues to possible inclusion of the NR3A subunit in NMDARs in many brain regions...
  73. pmc Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons
    Anton Ivanov
    INMED INSERM Unite 29, 163 Route de Luminy, 13009 Marseille, France
    J Physiol 572:789-98. 2006
    ..The negative regulation of the ERK activity might be one of the first signalling events determining brain injury and constitutes a putative target of new pharmacological applications...
  74. ncbi Coupling of extrasynaptic NMDA receptors to a CREB shut-off pathway is developmentally regulated
    Giles E Hardingham
    Department of Preclinical Veterinary Sciences, Royal Dick School of Veterinary Studies, Edinburgh University, Summerhall, EH9 1QH, Edinburgh, UK
    Biochim Biophys Acta 1600:148-53. 2002
    ....
  75. ncbi Miniature neurotransmission stabilizes synaptic function via tonic suppression of local dendritic protein synthesis
    Michael A Sutton
    Division of Biology 114 96, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 125:785-99. 2006
    ..These results indicate that NMDAR signaling during miniature synaptic transmission serves to stabilize synaptic function through active suppression of dendritic protein synthesis...
  76. ncbi Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine
    Fernanda G De Felice
    Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 282:11590-601. 2007
    ....
  77. ncbi Modular competition driven by NMDA receptor subtypes in spike-timing-dependent plasticity
    Richard C Gerkin
    Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
    J Neurophysiol 97:2851-62. 2007
    ..Using a simple model, we show that such a modular competition recapitulates our observations...
  78. ncbi Pathologically activated therapeutics for neuroprotection
    Stuart A Lipton
    Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California at San Diego 10901 North Torrey Pines Road, La Jolla, California 29, 037, USA
    Nat Rev Neurosci 8:803-8. 2007
    ..This approach has already met with success, and has led to the development of the potentially neuroprotective drug memantine, an N-methyl-D-aspartate (NMDA)-type and glutamate receptor antagonist...
  79. ncbi Compartmentalized dendritic plasticity and input feature storage in neurons
    Attila Losonczy
    Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Dr Ashburn, Virginia 20147, USA
    Nature 452:436-41. 2008
    ....
  80. pmc In developing hippocampal neurons, NR2B-containing N-methyl-D-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death
    M A Martel
    Centre for Neuroscience Research, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh EH8 9XD, UK
    Neuroscience 158:334-43. 2009
    ..In this instance, subunit differences cannot account for the dichotomous nature of NMDA receptor signaling...
  81. ncbi NMDA spikes in basal dendrites of cortical pyramidal neurons
    J Schiller
    Department of Physiology and Biophysics, Technion Medical School, Bat Galim, Haifa, Israel
    Nature 404:285-9. 2000
    ..In addition, NMDA spikes may serve as a powerful mechanism for modification of the cortical network by inducing long-term strengthening of co-activated neighbouring inputs...
  82. ncbi Novel presynaptic mechanisms for coincidence detection in synaptic plasticity
    Ian Duguid
    Wolfson Institute for Biomedical Research and Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK
    Curr Opin Neurobiol 16:312-22. 2006
    ..Recent studies also indicate the existence of presynaptic coincidence detection that is independent of NMDA receptors, suggesting that such mechanisms have a widespread role in plasticity...
  83. pmc Sensory processing in schizophrenia: neither simple nor intact
    Daniel C Javitt
    Department of Psychiatry, New York University Langone School of Medicine, Schizophrenia Research Center, Nathan Kline Institute for Psychiatric Research NYU School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Schizophr Bull 35:1059-64. 2009
    ..These studies also underscore the severe challenges that individuals with schizophrenia face when trying to decode the complex world around them...
  84. ncbi NMDA receptors in layer 4 spiny stellate cells of the mouse barrel cortex contain the NR2C subunit
    Alexander M Binshtok
    Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 76100, Israel
    J Neurosci 26:708-15. 2006
    ....
  85. ncbi A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy
    Melissa M Norberg
    Institute of Living, New Haven, CT 06106, USA
    Biol Psychiatry 63:1118-26. 2008
    ..This article provides a quantitative review of DCS-augmented fear extinction and exposure therapy literature...
  86. ncbi Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions
    Daniel C Javitt
    Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric, Research, New York University School of Medicine, Orangeburg, New York 10962, USA
    Int Rev Neurobiol 78:69-108. 2007
    ..Finally, genetic linkage and in vivo neurochemical studies in schizophrenia highlight potential etiological mechanisms giving rise to glutamatergic/NMDA dysfunction in schizophrenia...
  87. ncbi Induction of synaptic long-term potentiation after opioid withdrawal
    Ruth Drdla
    Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria
    Science 325:207-10. 2009
    ..These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia...
  88. ncbi Long-term potentiation and memory
    M A Lynch
    Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland
    Physiol Rev 84:87-136. 2004
    ....
  89. ncbi Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system--too little activation is bad, too much is even worse
    Chris G Parsons
    Merz Pharmaceuticals, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany
    Neuropharmacology 53:699-723. 2007
    ....
  90. ncbi LTP maintenance and its protein synthesis-dependence
    Wickliffe C Abraham
    Department of Psychology, University of Otago, Box 56, 95 Union Street, Dunedin 9016, New Zealand
    Neurobiol Learn Mem 89:260-8. 2008
    ..However, we highlight areas of research that could be usefully conducted to further our understanding of the properties and protein synthesis-dependence of LTP...
  91. ncbi Ionotropic and metabotropic glutamate receptor structure and pharmacology
    James N C Kew
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK
    Psychopharmacology (Berl) 179:4-29. 2005
    ..The development of selective ligands, including competitive agonists and antagonists and positive and negative allosteric modulators, has enabled investigation of the functional roles of glutamate receptor family members...
  92. pmc Spinophilin regulates the formation and function of dendritic spines
    J Feng
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 97:9287-92. 2000
    ..In conclusion, spinophilin appears to be required for the regulation of the properties of dendritic spines...
  93. pmc Single-channel activations and concentration jumps: comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors
    D J Wyllie
    Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
    J Physiol 510:1-18. 1998
    ..However, the latter were rather variable and some were slower than predicted. Slow decays were associated with patches that had large currents...
  94. ncbi Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking
    Myung Jong Kim
    The Picower Center for Learning and Memory, RIKEN MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Neuron 46:745-60. 2005
    ..Preferential coupling of NR2B to SynGAP could explain the subtype-specific function of NR2B-NMDARs in inhibition of Ras-ERK, removal of synaptic AMPARs, and weakening of synaptic transmission...
  95. ncbi Changing subunit composition of heteromeric NMDA receptors during development of rat cortex
    M Sheng
    Howard Hughes Medical Institute, University of California, San Francisco 94143 0724
    Nature 368:144-7. 1994
    ..A progressive alteration in subunit composition seen postnatally could contribute to NMDA-receptor variation and changing synaptic plasticity during cortical development...
  96. pmc IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats
    Rui Xin Zhang
    Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
    Pain 135:232-9. 2008
    ..05) and inhibited NR1 phosphorylation compared to saline control. The results suggest that spinal IL-1beta is produced by astrocytes and enhances NR1 phosphorylation to facilitate inflammatory pain...
  97. pmc Extrasynaptic and synaptic NMDA receptors form stable and uniform pools in rat hippocampal slices
    Alexander Z Harris
    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave, K426, Bronx, NY 10461, USA
    J Physiol 584:509-19. 2007
    ..Our data suggest that any role played by extrasynaptic NMDARs in synaptic transmission is dictated by their subcellular location rather than their subunit composition or mobility...
  98. ncbi Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors
    I Perez-Otano
    Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Neurosci 21:1228-37. 2001
    ..Our data demonstrate a role for subunit oligomerization and specifically assembly with the NR1 subunit in the trafficking and plasma membrane targeting of the receptor complex...
  99. ncbi Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus
    Larissa Lapteva
    Sjögren s Syndrome Clinic, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA
    Arthritis Rheum 54:2505-14. 2006
    ..To assess the association of cognitive dysfunction and depression with serum antibodies to N-methyl-D-aspartate (NMDA) receptor (anti-NR2) and analyze clinical and neuroimaging correlates in patients with systemic lupus erythematosus (SLE)...
  100. pmc Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2
    Takashi Nishimura
    Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466 8550, Japan
    Mol Biol Cell 17:1273-85. 2006
    ..Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation. These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2...
  101. ncbi A hippocampal NR2B deficit can mimic age-related changes in long-term potentiation and spatial learning in the Fischer 344 rat
    Daniel A Clayton
    Medical Scientist Training Program, Neuroscience Program, and Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Neurosci 22:3628-37. 2002
    ..These data demonstrate the important role of NR2B in LTP and learning and memory and suggest a role for reduced NR2B expression in age-related cognitive decline...

Research Grants62

  1. Predictors of Pregnancy Outcome in SLE and APS
    Jane E Salmon; Fiscal Year: 2012
    ....
  2. Presynaptic NMDAR Regulation of Substance P Release in the RVM After Injury
    UCHECHUKWU PATRICK MADUKA; Fiscal Year: 2013
    ....
  3. Central Mechanisms of Orofacial Pain
    Jianren Mao; Fiscal Year: 2012
    ..The outcome of this study could lead to the development of new therapeutic tools to treat often intractable and debilitating clinical orofacial pain. ..
  4. PRESYNAPTIC LONG-TERM SYNAPTIC DEPRESSION
    Patric K Stanton; Fiscal Year: 2012
    ..The long-term regulation of transmitter release has far-reaching importance to normal synaptic processing dynamics, and controlling pathologic glutamate release during injury or disease. ..
  5. Dynamics of pH Regulation in the Brain
    Mitchell Chesler; Fiscal Year: 2013
    ....
  6. HCN Channel Trafficking in Epilepsy
    Dane M Chetkovich; Fiscal Year: 2012
    ....
  7. Glial-cytokine-neuronal interactions in the mechanisms of persistent pain
    Ke Ren; Fiscal Year: 2012
    ..The outcome of these studies will enhance our understanding of functional linkage between the immune and nervous system and help to identify novel targets and agents for management of chronic pain. ..
  8. Expansion of intracranial hemorrhage by tPA after traumatic brain injury
    ABD ALROOF HIGAZI; Fiscal Year: 2013
    ..We will test these tPA variants and use mice with genetic deletion of tPA to provide insight into the pathogenesis of progressive ICH post TBI and to develop novel therapeutic interventions. ..
  9. The Role of Gliotransmission in Cerebral Ischemia
    Shinghua Ding; Fiscal Year: 2013
    ..Results from this project will derive entirely new insights into the causes of ischemia-induced neurodegeneration. ..
  10. Synaptic targeting and regulation of NMDAR subunits
    JOHN ALAN GRAY; Fiscal Year: 2013
    ....
  11. Permeation, Block, and Gating of NMDA Receptors
    Jon W Johnson; Fiscal Year: 2013
    ..The goal is to understand the important differences between the actions of the drugs to provide insight into the drug characteristics that allow one to help Alzheimer's disease patients, and the other to mimic schizophrenia. ..
  12. Modulation of Hippocampal Synaptic Plasticity
    Charles F Zorumski; Fiscal Year: 2013
    ..Our long-term goal is to identify ways to preserve and restore synaptic function in individuals with neuropsychiatric illnesses. ..
  13. GATING KINETICS OF GLYCINERGIC NMDA RECEPTORS
    KIRSTIE ALYSSA CUMMINGS; Fiscal Year: 2013
    ..Insights from this proposal will spur rational hypotheses to address these gaps in knowledge and will afford a more comprehensive understanding of the underlying molecular mechanism of the pathophysiology of schizophrenia. ..
  14. Structure and Function of NMDA Receptors
    Vasanthi Jayaraman; Fiscal Year: 2013
    ..These functional and structural investigations will provide a comprehensive understanding of the mechanism by which agonists and modulators mediate NMDA receptor function. ..
  15. MECHANISMS UNDERLYING ADRENAL STEROID MODULATION OF LTP
    Constantine Pavlides; Fiscal Year: 2000
    ..Understanding the mechanisms underlying their effects on synaptic plasticity will greatly enhance out understanding of how they may be involved in human disease. ..
  16. Rationally Designing Subunit Selective Antagonists for NR2C/D containing NMDA rec
    Timothy M Acker; Fiscal Year: 2012
    ..These studies will provide first in class subunit-selective pharmacological tools that will aid in furthering our understanding of the physiological and patho-physiological roles played by different NMDA receptors. ..
  17. mu Opioid Receptor Function in the Enteric Nervous System
    Catia Sternini; Fiscal Year: 2007
    ..abstract_text> ..
  18. MOLECULAR STUDIES OF BRAIN NMDA RECEPTORS
    R Suzanne Zukin; Fiscal Year: 2009
    ..Findings from the proposed studies are relevant to our understanding of these devastating and often fatal disorders. ..
  19. MECHANISMS OF APOPTOTIC DEATH IN DOPAMINERGIC NEURONS
    Anna Liisa Nieminen; Fiscal Year: 2003
    ..These experiments will yield new information to improve therapy of Parkinson s disease and to prevent the disease s progression. ..
  20. Steroids-Functional Modulators of Amino Acid Receptors
    DAVID FARB; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  21. Model Neuron Encoding the Realistic Learning Rule
    Makoto Nishiyama; Fiscal Year: 2006
    ..These studies will contribute significantly to our understanding the cellular and molecular basis of learning and memory. [unreadable] [unreadable]..
  22. FOLIC ACID AND HOMOCYSTEINE: MECHANISMS OF HEART DEFECTS
    Thomas Rosenquist; Fiscal Year: 2005
    ..Project 4 will test the elements of each of these hypotheses in a population-based study. ..
  23. INTRACELLULAR CATIONS AND EXCITOTOXICITY
    Ian Reynolds; Fiscal Year: 2002
    ....
  24. Activity Dependent Modulation of SK2 Channels
    Mike Lin; Fiscal Year: 2009
    ..This proposal is targeted to study the basic mechanisms of synaptic plasticity and memory formation, and will contribute to our fundamental knowledge in plasticity and learning process. ..
  25. Mechanisms of Ethanol Action on NMDA Receptors and LTP
    Rachel Linger; Fiscal Year: 2004
    ..Biochemical methods will be employed to evaluate the surface expression of NMDARs. We hope that these studies will contribute to the understanding of alcoholism by enhancing our knowledge of how ethanol affects cognition. ..
  26. N-methyl-D-aspartate Receptors in the Enteric Nervous System
    ARSEIMA DEL VALLE PINERO; Fiscal Year: 2008
    ..The identification of the NMDA receptors in the enteric nervous system could lead to the development of drugs that selectively modulate bowel function. [unreadable] [unreadable] [unreadable]..
  27. Phencyclidine Abuse & Psychosis: Biomedical Mechanisms
    Daniel C Javitt; Fiscal Year: 2010
    ....
  28. MECHANISMS OF COGNITIVE DYSFUNCTION IN SCHIZOPHRENIA
    Daniel Javitt; Fiscal Year: 2005
    ..This study will evaluate neurophysiological and neurochemical hypotheses concerning potential etiology of early sensory processing dysfunction in schizophrenia. ..
  29. High-Density ERP mapping & FMRI
    Daniel Javitt; Fiscal Year: 2002
    ..The equipment will also permit monitoring of background EEG during both human and animal studies. Software is requested for state-of-the-art ERP dipole mapping and ERP/MRI co-registration. ..
  30. TREATMENT OF NEGATIVE SYMPTOMS AND COGNITIVE IMPAIRMENTS
    Daniel Javitt; Fiscal Year: 2003
    ..The study will provide new information on the efficacy of d-cycloserine and glycine for both persistent primary and secondary negative symptoms and its effect on cognitive functioning. ..
  31. Antipsychotic Actions in Models of NMDA Hypofunction
    Gary Duncan; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  32. ELEMENTARY SCHOOL NEUROSCIENCE LITERACY
    Gary Duncan; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  33. NEUROPHYSIOLOGICAL NMDA DYSFUNCTION IN SCHIZOPHRENIA
    Daniel Javitt; Fiscal Year: 2006
    ..The research will build upon studies currently supported by NIH research and career development awards to the candidate, and will permit the candidate to continue to devote >75 percent effort to research. ..
  34. AIDS-Related Neurotoxicity and Novel NMDAR Antagonists
    Stuart Lipton; Fiscal Year: 2009
    ..It is anticipated that these preclinical studies investigating the role of the NMDAR in neuronal cell injury may lead to new treatments for the neurological manifestations of AIDS. ..
  35. Erythropoietin PLUS IGF-IN NEUROPROTECTION FROM AIDS
    Stuart Lipton; Fiscal Year: 2009
    ..Hypothesis Tested: EPO+IGF-I act synergistically to activate the anti-apoptotic PI3 kinase/Akt signaling pathway, and thus provide a synergistic degree of neuroprotection. ..
  36. RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERS
    Stuart A Lipton; Fiscal Year: 2010
    ..To characterize the ligand-binding site of NR3-containing receptors, and use information from [2] and [3] to distinguish expression of NR1/NR3 "doublet" receptors from NR1/NR2/NR3 "triplet" receptors on RGCs. ..
  37. ERYTHROPOIETIN-INDUCED NEUROPROTECTION
    Stuart Lipton; Fiscal Year: 2005
    ....
  38. Chemokines and Macrophages in HIV Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2003
    ..Neuronal apoptosis due to gp120 or chemokines will be monitored using several approaches. ..
  39. ETHANOL SENSITIVITY OF NATIVE AND CLONED NMDA RECEPTORS
    John Woodward; Fiscal Year: 2009
    ..Aim 3 will express ethanol-insensitive receptors identified in Aims 1 and 2 in neurons in vitro and in vivo to address which effects of ethanol are mediated by inhibition of NMDA receptors. ..
  40. Caspase Cleavage of MEF2 Mediates Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2007
    ....
  41. Ethanol sensitivity--native /recombinant NMDA receptors
    John Woodward; Fiscal Year: 2006
    ..The successful completion of this training plan will substantially enhance the PI's research expertise and his ability to fulfill the goals of his research. ..
  42. S-Nitrosylation of Matrix Metalloproteinases in AIDS
    Stuart Lipton; Fiscal Year: 2007
    ..In the future, the work proposed here may lead to new therapeutic targets based on the novel extracellular signaling pathway involving NO-related molecules and the MMPs that will be studied. ..
  43. Neurobiology of Spatial Reversal Learning
    Deborah Watson; Fiscal Year: 2008
    ..These goals serve the mission of a variety of NIH agencies (e.g., NICHD, NIMH, NIDA, NIHS, and NIAAA). [unreadable] [unreadable] [unreadable]..
  44. Escalating Cocaine Self-Administration: NMDA Mechanisms
    Richard Allen; Fiscal Year: 2003
    ..abstract_text> ..
  45. Protein Kinase C Modulation of NMDAR Ethanol Sensitivity
    ROSEANNA POPP; Fiscal Year: 2006
    ..Thus, facilitating the future design of novel therapeutic strategies to be used in the treatment of alcoholism and alcohol abuse...
  46. Calcium Homeostasis and Neonatal Brain Injury
    Christopher Turner; Fiscal Year: 2009
    ....
  47. Novel pharmacotherapies for treatment of ADHD
    FRANK TARAZI; Fiscal Year: 2003
    ..Expected findings should evolve new principles and lead to novel compounds that can be used as much-needed innovative treatments for ADHD and other major neuropsychiatric disorders. ..
  48. DEVELOPMENTAL PLASTICITY AND CHRONIC EPILEPSY
    John Swann; Fiscal Year: 2007
    ..Since there are so few animal models of early-onset epilepsy, the studies proposed here offer a unique opportunity to further an understanding of the biological origins of seizure disorders in infancy. ..
  49. Peripheral and Central Mechanism of Pain in Patients with Fibromyalgia
    ROLAND M STAUD; Fiscal Year: 2010
    ..Either way, we will provide evidence that will characterize the role of local anesthesia, placebo analgesia, or both. Thus patients with FM and other similar pain syndromes may strongly benefit from the results of our study. ..
  50. Cellular and Molecular Mechanisms of Learning in the Zebrafish
    David Glanzman; Fiscal Year: 2007
    ..Such an understanding will facilitate the development of treatments for Alzheimer's disease and other disorders of memory. [unreadable] [unreadable] [unreadable]..
  51. Alcohol and Developing Neuronal Circuits
    CARLOS VALENZUELA; Fiscal Year: 2009
    ..Collectively, these studies will establish that network neuronal activity driven by the excitatory actions of GABAA is a novel and important target of the actions of EtOH during hippocampal development. ..
  52. Pre and Postsynaptic Consequences of Traumatic CNS Injury
    Scott M Thompson; Fiscal Year: 2011
    ..Project Narrative: We seek to discover the causes of the form of epilepsy that occurs after a severe head injury and to develop new therapies to treat or prevent this condition. ..
  53. BRAIN AND SPINAL CORD CONTRIBUTIONS TO ANESTHETIC ACTION
    JOSEPH ANTOGNINI; Fiscal Year: 2005
    ..This information will aid the development of newer and safer anesthetics, as well as lead to clinically useful means of modulating the neurotransmitter systems that are themselves modulated by anesthetics. ..
  54. NALTREXONE BLOCKADE OF NMDA
    John Krystal; Fiscal Year: 2002
    ..Thus, the blockade of the rewarding effects of ketamine by naltrexone may provide insight into an important mechanism underlying the psychopharmacology of ethanol and the treatment of alcoholism. ..
  55. Neuropharmacology of GHB discrimination
    Wouter Koek; Fiscal Year: 2010
    ..Increased knowledge about the activation and modulation of GABAB systems will help to develop effective approaches to treating sleep-, drug abuse-, and other CNS disorders. ..
  56. Marine Toxin Impacts on Neurobehavioral Function
    Edward Levin; Fiscal Year: 2003
    ..The forum will provide an opportunity for methodological and theoretical issues to be integrated in the context of each talk as well as in a discussion session at the end of the symposium. ..
  57. NMDA Receptor Dynamics After Brain Injury
    Anat Biegon; Fiscal Year: 2011
    ..The results may explain the failure of NMDAR antagonists in clinical trials and suggest novel strategies for treatment of brain injury. ..
  58. Signaling cascades and memory deficits during aging
    Thomas C Foster; Fiscal Year: 2010
    ..The long range goal is to provide interventions to delay, prevent, or treat cognitive decline associated with unsuccessful aging in order to improve the health and well- being of older Americans ..
  59. Cellular and Molecular Basis of Long-Term Habituation
    David Glanzman; Fiscal Year: 2007
    ..Such an understanding will facilitate the development of treatments of diseases of memory, such as Alzheimer's. ..
  60. Axonal Sprouting of GABAergic Neurons in Epileptogenesis
    SUZANNE BAUSCH; Fiscal Year: 2004
    ..abstract_text> ..
  61. AMINO ACID NEUROTRANSMITTER DYSREGULATION IN ALCOHOLISM
    John Krystal; Fiscal Year: 2008
    ..abstract_text> ..
  62. Norepinephrine Transporters: Targets for ADHD
    FRANK TARAZI; Fiscal Year: 2004
    ..Expected findings should lead to novel compounds that can be developed as much needed innovative non-stimulant treatments for ADHD and other major neuropsychiatric disorders. ..