gaba a receptors

Summary

Summary: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and control an integral membrane chloride channel. GABA-A receptors are the most prevalent inhibitory neurotransmitter receptors in the brain. Several isoforms have been cloned, and they belong to a superfamily which includes nicotinic receptors, glycine receptors, and 5HT-3 receptors. Most GABA-A receptors have separate modulatory sites sensitive to benzodiazepines and to barbiturates.

Top Publications

  1. ncbi Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors
    Mark Farrant
    Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
    Nat Rev Neurosci 6:215-29. 2005
  2. ncbi Tonically active GABA A receptors: modulating gain and maintaining the tone
    Alexey Semyanov
    Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    Trends Neurosci 27:262-9. 2004
  3. ncbi GABA uptake regulates cortical excitability via cell type-specific tonic inhibition
    Alexey Semyanov
    Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    Nat Neurosci 6:484-90. 2003
  4. ncbi Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance
    S G Brickley
    Department of Pharmacology, University College London, London WC1E 6BT, UK
    Nature 409:88-92. 2001
  5. pmc Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors
    Valerie B Caraiscos
    Institute of Medical Science, Department of Anesthesia, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 101:3662-7. 2004
  6. ncbi Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells
    Zoltan Nusser
    Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095 1769, USA
    J Neurophysiol 87:2624-8. 2002
  7. ncbi Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons
    D Bai
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Mol Pharmacol 59:814-24. 2001
  8. ncbi Specific GABAA circuits for visual cortical plasticity
    Michela Fagiolini
    Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama, 351 0198 Japan
    Science 303:1681-3. 2004
  9. ncbi The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon
    W Wisden
    Laboratory of Molecular Neuroendocrinology, Zentrum fur Molekulare Biologie, University of Heidelberg, Germany
    J Neurosci 12:1040-62. 1992
  10. pmc GABA A receptors: subtypes provide diversity of function and pharmacology
    Richard W Olsen
    Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1735, USA
    Neuropharmacology 56:141-8. 2009

Research Grants

  1. Efficacy of GABAA a5 receptor inverse agonists in learning impaired rats
    EARL MICHAEL GIBBS; Fiscal Year: 2010
  2. GABA chaperoning of epilepsy-associated GABAA receptor mutants.
    Nancy J Leidenheimer; Fiscal Year: 2012
  3. Neuroplasticity with alcohol dependence
    Scott C Steffensen; Fiscal Year: 2013
  4. CODING IN AUDITORY NEURONS: EFFECTS OF AMINO ACIDS
    Donald M Caspary; Fiscal Year: 2013
  5. Estrogen and TMJ Pain
    Phillip R Kramer; Fiscal Year: 2013
  6. Variations in Hormones During Menopause: Effects on Cognitive and Brain Aging
    Heather A Bimonte-Nelson; Fiscal Year: 2013
  7. Functional Anatomy of REM Sleep: Brainstem-Control
    Gerald A Marks; Fiscal Year: 2013
  8. Structural Rearrangements in GABA-A Receptors
    CYNTHIA M CZAJKOWSKI; Fiscal Year: 2012
  9. General Anesthetic Sites in GABA-A Receptor Subunit Interfacial Pockets
    Stuart A Forman; Fiscal Year: 2013
  10. Hyperpolarized 129-Xenon-based MRI Probes for Brain Injury
    JEREMY PHILLIP CELVER; Fiscal Year: 2010

Detail Information

Publications308 found, 100 shown here

  1. ncbi Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors
    Mark Farrant
    Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
    Nat Rev Neurosci 6:215-29. 2005
    ..In this review, we consider the distinct roles of synaptic and extrasynaptic GABA receptor subtypes in the control of neuronal excitability...
  2. ncbi Tonically active GABA A receptors: modulating gain and maintaining the tone
    Alexey Semyanov
    Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    Trends Neurosci 27:262-9. 2004
    ....
  3. ncbi GABA uptake regulates cortical excitability via cell type-specific tonic inhibition
    Alexey Semyanov
    Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    Nat Neurosci 6:484-90. 2003
    ..Reducing the tonic conductance in interneurons enhanced their excitability and the inhibitory drive to pyramidal cells. These results point to a role for cell type-dependent tonic inhibition in regulating cortical excitability...
  4. ncbi Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance
    S G Brickley
    Department of Pharmacology, University College London, London WC1E 6BT, UK
    Nature 409:88-92. 2001
    ....
  5. pmc Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors
    Valerie B Caraiscos
    Institute of Medical Science, Department of Anesthesia, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 101:3662-7. 2004
    ....
  6. ncbi Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells
    Zoltan Nusser
    Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095 1769, USA
    J Neurophysiol 87:2624-8. 2002
    ..Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function...
  7. ncbi Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons
    D Bai
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Mol Pharmacol 59:814-24. 2001
    ..In summary, the receptors underlying the tonic current are functionally and pharmacologically distinct from quantally activated synaptic receptors and these receptors represent a novel target for neurodepressive drugs...
  8. ncbi Specific GABAA circuits for visual cortical plasticity
    Michela Fagiolini
    Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama, 351 0198 Japan
    Science 303:1681-3. 2004
    ..This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants...
  9. ncbi The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon
    W Wisden
    Laboratory of Molecular Neuroendocrinology, Zentrum fur Molekulare Biologie, University of Heidelberg, Germany
    J Neurosci 12:1040-62. 1992
    ..Based on significant mismatches between alpha 4/delta and gamma mRNAs, we suggest that in vivo, the alpha 4 subunit contributes to GABAA receptors that lack BZ modulation...
  10. pmc GABA A receptors: subtypes provide diversity of function and pharmacology
    Richard W Olsen
    Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1735, USA
    Neuropharmacology 56:141-8. 2009
    ..This list was first presented by Olsen & Sieghart (in press)...
  11. ncbi Activation of GABAA receptors: views from outside the synaptic cleft
    Joseph Glykys
    Interdepartmental PhD Program for Neuroscience, The David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA
    Neuron 56:763-70. 2007
    ..These same receptors constitute important and specific targets for various endogenous and exogenous neuroactive compounds and possible therapeutic targets...
  12. ncbi Drug interactions at GABA(A) receptors
    Esa R Korpi
    Department of Pharmacology and Clinical Pharmacology, University of Turku, Itainen Pitkakatu 4B, Finland
    Prog Neurobiol 67:113-59. 2002
    ....
  13. ncbi Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement
    Sabine W Baumann
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Biol Chem 277:46020-5. 2002
    ..The methods established here should be applicable to the entire ion channel family comprising nicotinic acetylcholine, glycine, and 5HT(3) receptors...
  14. ncbi Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABA A receptor alpha5 subunit-deficient mice
    Joseph Glykys
    Interdepartmental PhD Program for Neuroscience and Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA
    J Neurophysiol 95:2796-807. 2006
    ....
  15. ncbi Novel compounds selectively enhance delta subunit containing GABA A receptors and increase tonic currents in thalamus
    K A Wafford
    Department of Molecular and Cellular Neuroscience, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, United Kingdom
    Neuropharmacology 56:182-9. 2009
    ..Furthermore, these drugs may be valuable in elucidating the physiological and pathophysiological roles played by these extrasynaptic GABA(A) receptors...
  16. pmc Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier
    M W McEnery
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2185
    Proc Natl Acad Sci U S A 89:3170-4. 1992
    ..VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes...
  17. pmc Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning
    Peer Wulff
    Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, UK
    Nat Neurosci 12:1042-9. 2009
    ....
  18. ncbi Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain
    T Philip Malan
    Department of Anesthesiology, The University of Arizona, Tucson, Arizona 85724 5114, USA
    Anesthesiology 96:1161-7. 2002
    ..This study tests the hypothesis that loss of spinal activity of gamma-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury...
  19. ncbi Excitatory actions of GABA in the cortex
    Allan T Gulledge
    Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Mills Road, Canberra, ACT 0200, Australia
    Neuron 37:299-309. 2003
    ..Our findings demonstrate that under certain circumstances GABA will have an excitatory role in synaptic integration in the cortex...
  20. pmc Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates
    James K Rowlett
    Harvard Medical School, New England Primate Research Center, One Pine Hill Road, Box 9102, Southborough, MA 01772, USA
    Proc Natl Acad Sci U S A 102:915-20. 2005
    ..In contrast, stimulation of alpha1GABAA receptors is sufficient, but not necessary, for mediation of the abuse potential of these drugs...
  21. pmc Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors
    N Brown
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Br J Pharmacol 136:965-74. 2002
    ..With its restricted distribution within the brain and unique pharmacology this receptor may play an important role in the action of neurosteroids and anaesthetics. British Journal of Pharmacology (2002) 136, 965-974..
  22. ncbi Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function
    Vassilios Papadopoulos
    Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20057, USA
    Trends Pharmacol Sci 27:402-9. 2006
    ..Translocator protein (18kDa) is proposed as a new name, regardless of the subcellular localization of the protein...
  23. ncbi Identified sources and targets of slow inhibition in the neocortex
    Gabor Tamas
    Department of Comparative Physiology, University of Szeged, Közép fasor 52, Szeged H 6726, Hungary
    Science 299:1902-5. 2003
    ..Slow inhibition evoked by a distinct interneuron in spatially restricted postsynaptic compartments could locally and selectively modulate cortical excitability...
  24. ncbi Change in mRNAs for neuropeptides and the GABA(A) receptor in dorsal root ganglion neurons in a rat experimental neuropathic pain model
    T Fukuoka
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Japan
    Pain 78:13-26. 1998
    ....
  25. ncbi A point mutation in a Drosophila GABA receptor confers insecticide resistance
    R H ffrench-Constant
    Department of Entomology, 237 Russell Laboratories, University of Wisconsin, Madison 53706
    Nature 363:449-51. 1993
    ....
  26. ncbi A single histidine in GABAA receptors is essential for benzodiazepine agonist binding
    H A Wieland
    Laboratory of Molecular Neuroendocrinology, University of Heidelberg, Germany
    J Biol Chem 267:1426-9. 1992
    ..Hence, this histidine present in the alpha 1, alpha 2, alpha 3, and alpha 5 subunits appears to be a key residue for the action of clinically used BZ ligands...
  27. pmc Cl- uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1
    Junko Yamada
    Department of Biological Information Processing, Graduate School of Electronic Science and Technology, Shizuoka University, Hamamatsu, Shizuoka 432 8011, Japan
    J Physiol 557:829-41. 2004
    ..These data suggest that NKCC1 may play a pivotal role in the generation of GABA-mediated depolarization in immature CP cells, while KCC2 promotes the later maturation of GABAergic inhibition in the rat neocortex...
  28. ncbi Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor
    B Antkowiak
    Max Planck Institut für biologische Kybernetik, Tubingen, Germany
    Anesthesiology 91:500-11. 1999
    ..The author's aim was to determine if other anesthetic agents are similarly effective in this model system and act via the same molecular mechanism...
  29. ncbi Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo
    Didier Decaudin
    Department of Hematology, and UMR 147 CNRS, Section de Recherche, Institut Curie, 75005 Paris, France
    Cancer Res 62:1388-93. 2002
    ..Peripheral benzodiazepine receptor ligands may therefore act as chemosensitizing agents for the treatment of human neoplasms...
  30. ncbi An extrasynaptic GABAA receptor mediates tonic inhibition in thalamic VB neurons
    Fan Jia
    CV Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College, Cornell University, New York, NY 10021, USA
    J Neurophysiol 94:4491-501. 2005
    ..In view of the critical role of thalamic neurons in the generation of oscillatory activity associated with sleep, these receptors may represent a principal site of action for the novel hypnotic agent gaboxadol...
  31. ncbi Synaptic release generates a tonic GABA(A) receptor-mediated conductance that modulates burst precision in thalamic relay neurons
    Damian P Bright
    Biophysics Section, Blackett Laboratory, Imperial College, London SW7 2AZ, United Kingdom
    J Neurosci 27:2560-9. 2007
    ..Hence, activation of delta-GABA(A)Rs could act to destabilize thalamocortical oscillations and therefore have an important impact on behavioral state...
  32. ncbi Physiological and structural evidence for hippocampal involvement in persistent seizure susceptibility after traumatic brain injury
    G Golarai
    Department of Neurosciences, University of New Mexico, Albuquerque, New Mexico 87131 5223, USA
    J Neurosci 21:8523-37. 2001
    ....
  33. ncbi Role of GABA in anxiety and depression
    Allan V Kalueff
    Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland, USA
    Depress Anxiety 24:495-517. 2007
    ..The role of GABAergic agents in demonstrating this interrelationship and in pointing the way to future research is discussed...
  34. ncbi Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit
    K A Wafford
    Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK
    Mol Pharmacol 50:670-8. 1996
    ..These experiments reveal a unique pharmacology for alpha 4-containing receptors with some similarities to both alpha 6- and alpha 1-containing receptors...
  35. ncbi Glucose inhibition of glucagon secretion from rat alpha-cells is mediated by GABA released from neighboring beta-cells
    Anna Wendt
    Department of Physiological Sciences, Lund University, Lund, Sweden
    Diabetes 53:1038-45. 2004
    ..This effect was not observed in the presence of SR95531, and we therefore conclude that isradipine stimulates glucagon secretion by inhibition of GABA release...
  36. ncbi Depolarizing GABA acts on intrinsically bursting pyramidal neurons to drive giant depolarizing potentials in the immature hippocampus
    Sampsa T Sipilä
    Department of Biological and Environmental Sciences, University of Helsinki, FIN 00014 Helsinki, Finland
    J Neurosci 25:5280-9. 2005
    ....
  37. pmc Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex
    A M Thomson
    Royal Free Hospital School of Medicine, London UK
    J Physiol 496:81-102. 1996
    ..An additional class, burst firing, spiny interneurones appear to activate GABAA receptors on more distal sites...
  38. ncbi Mechanisms of actions of inhaled anesthetics
    Jason A Campagna
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA
    N Engl J Med 348:2110-24. 2003
  39. ncbi Subunit arrangement of gamma-aminobutyric acid type A receptors
    S W Baumann
    Department of Pharmacology, University of Bern, , CH-3010 Bern, Switzerland
    J Biol Chem 276:36275-80. 2001
    ..Our findings also favor an arrangement betaalphagammabetaalpha for the receptor composed of alpha, beta, and gamma subunits...
  40. ncbi Defining the propofol binding site location on the GABAA receptor
    Moez Bali
    Department of Physiology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA
    Mol Pharmacol 65:68-76. 2004
    ..Propofol did not protect the cysteine substituted for the aligned alpha1 subunit position or the 15' M2 segment Cys mutants in either subunit. We infer that propofol may bind near the extracellular end of the betasubunit M3 segment...
  41. pmc Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors
    U Gunther
    Institute of Pharmacology, University of Zurich, Switzerland
    Proc Natl Acad Sci U S A 92:7749-53. 1995
    ..The lack of postnatal GABAA receptor regulation by endogenous ligands of BZ sites might contribute to this phenotype...
  42. ncbi The actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits
    Koichi Nishikawa
    Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi City, Japan
    Anesthesiology 99:678-84. 2003
    ..The aim of this study was to examine the effects of sevoflurane and desflurane on potentiation of GABA-induced responses in the wild-type GABAA receptor and in receptors mutated in TM2 of the alpha1, alpha 2, or beta 2 subunits...
  43. ncbi Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro
    H Wilms
    Klinik fur Neurologie, Christian Albrechts Universitat zu Kiel, Niemannsweg 147, 24105 Kiel, Germany
    Neurobiol Dis 14:417-24. 2003
    ..These findings link the in vivo data of elevated PBR levels in neurodegenerative/-inflammatory diseases to a functional role and opens up possible therapeutic intervention targeting the PBR in microglia...
  44. ncbi Synaptic alpha 5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex
    Afia B Ali
    Department of Pharmacology, School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Cereb Cortex 18:1260-71. 2008
    ....
  45. pmc GABA(B) receptor modulation of feedforward inhibition through hippocampal neurogliaform cells
    Christopher J Price
    Medical Research Council Anatomical Neuropharmacology Unit, Oxford OX1 3TH, United Kingdom
    J Neurosci 28:6974-82. 2008
    ..The NGFC-CA1 pyramidal cell connection therefore provides a unique and subtle mechanism to shape the integration time domain for signals arriving via a major excitatory input to CA1 pyramidal cells...
  46. ncbi Translational aspects of pharmacological research into anxiety disorders: the stress-induced hyperthermia (SIH) paradigm
    Christiaan H Vinkers
    Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences UIPS and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
    Eur J Pharmacol 585:407-25. 2008
    ..The SIH response is an autonomic stress response that can be successfully studied at the level of its physiology, pharmacology, neurobiology and genetics and possesses excellent animal-to-human translational properties...
  47. ncbi DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization
    Michelle L James
    Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia
    J Nucl Med 49:814-22. 2008
    ..Radioligands for the TSPO can therefore measure active disease in the brain. This article details the synthesis, radiofluorination, and pharmacologic evaluation of a new TSPO-specific pyrazolopyrimidine, DPA-714...
  48. ncbi Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus
    Annalisa Scimemi
    Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
    J Neurosci 25:10016-24. 2005
    ..The relative contribution of these components changes after the induction of epilepsy, implying an adaptive plasticity of the tonic current in the presence of spontaneous seizures...
  49. pmc International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update
    Richard W Olsen
    Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Room CHS 23 120, 650 Young Drive South, Los Angeles, CA 90095 1735, USA
    Pharmacol Rev 60:243-60. 2008
    ..The list is divided into three categories of native receptor subtypes: "identified," "existence with high probability," and "tentative."..
  50. ncbi Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus
    Shih Chun Lin
    Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe Street, WBSB 813, Baltimore, Maryland 21205, USA
    Nat Neurosci 7:24-32. 2004
    ....
  51. ncbi Association between a GABRB3 polymorphism and autism
    J D Buxbaum
    Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Mol Psychiatry 7:311-6. 2002
    ..These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder...
  52. ncbi Molecular and functional diversity of the expanding GABA-A receptor gene family
    P J Whiting
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, England, UK
    Ann N Y Acad Sci 868:645-53. 1999
    ..The structure, function, and distribution of theta-containing receptors, and receptors containing the recently reported epsilon subunit, are described...
  53. ncbi Extrasynaptic GABAA receptors of thalamocortical neurons: a molecular target for hypnotics
    Delia Belelli
    Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom
    J Neurosci 25:11513-20. 2005
    ..Collectively, these findings suggest that enhancement of extrasynaptic inhibition in the thalamus may contribute to the distinct sleep EEG profiles of etomidate and THIP compared with zolpidem...
  54. pmc Different transmitter transients underlie presynaptic cell type specificity of GABAA,slow and GABAA,fast
    Janos Szabadics
    Department of Anatomy and Neurobiology, University of California, 193 Irvine Hall, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 104:14831-6. 2007
    ..These results reveal a form of GABA(A) receptor mediated communication by a dedicated cell type that produces slow ionotropic responses with properties intermediate between phasic and tonic inhibition...
  55. pmc Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide
    H Li
    Division of Hormone Research, Departments of Cell Biology and Pharmacology and Neuroscience, Georgetown University School of Medicine, Washington, DC. 20007, USA
    Proc Natl Acad Sci U S A 98:1267-72. 2001
    ....
  56. ncbi Subunit composition, distribution and function of GABA(A) receptor subtypes
    W Sieghart
    Section of Biochemical Psychiatry, University Clinic for Psychiatry, and Department of Biochemistry and Molecular Biology, Brain Research Institute, University of Vienna, Vienna, Austria
    Curr Top Med Chem 2:795-816. 2002
    ..Such drugs might exhibit quite selective clinical effects...
  57. ncbi Neurosteroids shift partial agonist activation of GABA(A) receptor channels from low- to high-efficacy gating patterns
    Matt T Bianchi
    Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48104 1687, USA
    J Neurosci 23:10934-43. 2003
    ..Allosteric conversion of partial to full agonism may be a general mechanism for reversibly scaling the efficacy of GABA(A) receptors to endogenous partial agonists...
  58. ncbi Brain-derived neurotrophic factor (BDNF)-induced synthesis of early growth response factor 3 (Egr3) controls the levels of type A GABA receptor alpha 4 subunits in hippocampal neurons
    Daniel S Roberts
    Laboratory of Molecular Neurobiology, Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 281:29431-5. 2006
    ....
  59. ncbi Intact synaptic GABAergic inhibition and altered neurosteroid modulation of thalamic relay neurons in mice lacking delta subunit
    Darrell M Porcello
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurophysiol 89:1378-86. 2003
    ..This suggests delta subunit containing GABA(A) receptors may be functionally limited to an extrasynaptic locus in VB neurons...
  60. ncbi Visualising microglial activation in vivo
    Richard B Banati
    Department of Neuropathology, Charing Cross Hospital, Imperial College School of Medicine, and MRC Clinical Sciences Centre PET Neurology, Hammersmith Hospital, London, United Kingdom
    Glia 40:206-17. 2002
    ....
  61. pmc Corelease and differential exit via the fusion pore of GABA, serotonin, and ATP from LDCV in rat pancreatic beta cells
    Matthias Braun
    Oxford Center for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK
    J Gen Physiol 129:221-31. 2007
    ....
  62. ncbi Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificity
    S Khom
    Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A 1090 Vienna, Austria
    Neuropharmacology 53:178-87. 2007
    ..A possible open channel block mechanism is discussed. In summary, VA was identified as a subunit specific allosteric modulator of GABA(A) receptors that is likely to interact with the loreclezole binding pocket...
  63. pmc Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging
    Cedric Bouzigues
    Laboratoire Kastler Brossel, Centre National de la Recherche Scientifique, Physics Department, Ecole Normale Superieure, and Université Pierre et Marie Curie Paris 6, 24, rue Lhomond, 75005 Paris, France
    Proc Natl Acad Sci U S A 104:11251-6. 2007
    ..Altogether, our results reveal a microtubule-dependent polarized reorganization of chemoreceptors at the cell surface and suggest that this polarization serves as an amplification step in GABA gradient sensing by nerve GCs...
  64. ncbi Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: a TMS study
    V Di Lazzaro
    Institute of Neurology, Universita Cattolica, L go A Gemelli 8, 00168 Rome, Italy
    Clin Neurophysiol 118:2207-14. 2007
    ..To investigate if different interneuronal circuits in human motor cortex mediate inhibition through different subtypes of the gamma-aminobutyric acid A receptor (GABAAR)...
  65. ncbi Developing analgesics by enhancing spinal inhibition after injury: GABAA receptor subtypes as novel targets
    Gordon Munro
    Neurosearch A S, Ballerup DK 2750, Denmark
    Trends Pharmacol Sci 30:453-9. 2009
    ....
  66. ncbi Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus
    C Sur
    Department of Biochemistry and Molecular Biology, Neuroscience Research Centre, Merck Research Laboratories, Harlow, Essex, United Kingdom
    Mol Pharmacol 56:110-5. 1999
    ..In conclusion, our results show that in rat thalamus both alpha4betagamma2 and alpha4betadelta subtypes are expressed but alpha4betadelta is the major alpha4-containing GABAA receptor population...
  67. pmc Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia
    Takanori Hashimoto
    Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Am J Psychiatry 165:479-89. 2008
    ....
  68. ncbi Evidence for a significant role of alpha 3-containing GABAA receptors in mediating the anxiolytic effects of benzodiazepines
    Rebecca Dias
    The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Harlow, Essex CM20 2QR, United Kingdom
    J Neurosci 25:10682-8. 2005
    ..Together, these data show that potentiation of alpha3-containing GABA(A) receptors is sufficient to produce the anxiolytic effects of BZs and that alpha2 potentiation may not be necessary...
  69. ncbi Neuronal glutamate uptake Contributes to GABA synthesis and inhibitory synaptic strength
    Gregory C Mathews
    Synaptic Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 4066, USA
    J Neurosci 23:2040-8. 2003
    ..This modulation appears to occur under normal conditions and may constitute a negative feedback mechanism to combat hyperexcitability...
  70. ncbi Short communication: altered synaptic clustering of GABAA receptors in mice lacking dystrophin (mdx mice)
    I Knuesel
    Institute of Pharmacology, University of Zurich, Switzerland
    Eur J Neurosci 11:4457-62. 1999
    ..These deficits may underlie the cognitive impairment seen in Duchenne patients...
  71. ncbi GABAA receptor-mediated tonic inhibition in thalamic neurons
    David W Cope
    School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom
    J Neurosci 25:11553-63. 2005
    ..Thus, tonic current in TC neurons generates an inhibitory tone. Its modulation contributes to the shift between different firing modes, promotes the transition between different behavioral states, and predisposes to absence seizures...
  72. ncbi Extrasynaptic GABA(A) channels activated by THIP are modulated by diazepam in CA1 pyramidal neurons in the rat brain hippocampal slice
    Catarina E L Lindquist
    Molecular and Cellular Physiology, Department of Physiological Sciences, Lund University, Tornavagen 10 BMC F11, 22184 Lund, Sweden
    Mol Cell Neurosci 24:250-7. 2003
    ..5-5 microM ) of GABA. The increase in the inhibitory conductance with membrane depolarization permits gradation of the shunt pathway relative to the level of the excitatory input...
  73. ncbi Cerebellar GABAA receptor selective for a behavioural alcohol antagonist
    H Lüddens
    Centre for Molecular Biology, University of Heidelberg, FRG
    Nature 346:648-51. 1990
    ..We conclude that this alpha-subunit is part of a cerebellar receptor subtype, selective for Ro15-4513, an antagonist of alcohol-induced motor incoordination and ataxia...
  74. pmc Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl- and HCO3- transport
    K J Staley
    Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Physiol 519:693-712. 1999
    ..5. Using a standard model of membrane potential, these conditions are demonstrated to be sufficient to produce the experimentally observed, activity-dependent GABA(A) depolarizing response in pyramidal cell dendrites...
  75. ncbi cDNA cloning and expression of a gamma-aminobutyric acid A receptor epsilon-subunit in rat brain
    N Moragues
    Laboratoire de Neurophysiologie CNRS UMR 5543, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France
    Eur J Neurosci 12:4318-30. 2000
    ..Our results suggest that novel GABA(A) receptors may regulate, neuroendocrine and modulatory systems in the brain...
  76. ncbi Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster
    P J McLean
    Department of Pharmacology, Boston University School of Medicine, Massachusetts 02118, USA
    Genomics 26:580-6. 1995
    ....
  77. ncbi Localisation of GABA(A) receptor epsilon-subunit in cholinergic and aminergic neurones and evidence for co-distribution with the theta-subunit in rat brain
    N Moragues
    Laboratoire de Neurophysiologie CNRS UMR 5543, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux, France
    Neuroscience 111:657-69. 2002
    ....
  78. ncbi Multiple actions of propofol on alphabetagamma and alphabetadelta GABAA receptors
    Hua Jun Feng
    Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 8552, USA
    Mol Pharmacol 66:1517-24. 2004
    ....
  79. ncbi Abnormal GABAA receptor-mediated currents in dorsal root ganglion neurons isolated from Na-K-2Cl cotransporter null mice
    K W Sung
    Departments of Anesthesiology, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennesse, USA
    J Neurosci 20:7531-8. 2000
    ....
  80. ncbi Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology
    D B Pritchett
    Laboratory of Molecular Neuroendocrinology, Universitat Heidelberg, F R G
    J Neurochem 54:1802-4. 1990
    ..Based on these findings, a reclassification of the GABAA/benzodiazepine receptors is warranted...
  81. ncbi TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates
    John R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Pharmacol Exp Ther 316:410-22. 2006
    ..In summary, the novel alpha2/alpha3-selective efficacy profile of TPA023 translates into a nonsedating anxiolytic profile that is distinct from nonselective agonists...
  82. pmc Optimized expression vector for ion channel studies in Xenopus oocytes and mammalian cells using alfalfa mosaic virus
    Srinivasan P Venkatachalan
    Department of Physiology, University of Wisconsin Madison, 601 Science Drive, Madison, WI 53711, USA
    Pflugers Arch 454:155-63. 2007
    ..Furthermore, we found that expression using pUNIV was significantly enhanced in oocytes and was remarkably long-lasting in both systems...
  83. ncbi Consequences of the evolution of the GABA(A) receptor gene family
    Mark G Darlison
    Neuroscience and Signal Transduction Laboratory, School of Biomedical and Natural Sciences, College of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, United Kingdom
    Cell Mol Neurobiol 25:607-24. 2005
    ..We suggest that a possibly more important consequence of gene duplication is that it permitted greater flexibility in the level, pattern and regulation of expression of GABA(A) receptor genes...
  84. ncbi The GABAA receptor alpha 1 subunit Pro174-Asp191 segment is involved in GABA binding and channel gating
    J Glen Newell
    Department of Physiology, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Biol Chem 278:13166-72. 2003
    ....
  85. ncbi The gamma-aminobutyric acid receptor gamma 3 subunit gene (GABRG3) is tightly linked to the alpha 5 subunit gene (GABRA5) on human chromosome 15q11-q13 and is transcribed in the same orientation
    V Greger
    Genetics Division, Children s Hospital, Boston, MA 02115, USA
    Genomics 26:258-64. 1995
    ..The two genes are located within 35 kb of each other and are transcribed in the same orientation...
  86. ncbi Association of gephyrin with synaptic and extrasynaptic GABAA receptors varies during development in cultured hippocampal neurons
    Lydia Danglot
    Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique, Institut National de la Santé et de la Recherche Médicale U497, Ecole Normale Superieure, 75005, Paris, France
    Mol Cell Neurosci 23:264-78. 2003
    ..Subsequently, the GABAAR gamma2 subunits associated with gephyrin at synaptic and/or extrasynaptic sites. Our data indicate that formation of GABAAR gamma2 subunit clusters is gephyrin independent...
  87. ncbi GABAA receptors: building the bridge between subunit mRNAs, their promoters, and cognate transcription factors
    Janine L Steiger
    Laboratory of Molecular Neurobiology, Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118, USA
    Pharmacol Ther 101:259-81. 2004
    ..It is hoped that through this functional genomic approach there will be the identification of new targets for therapeutic intervention...
  88. ncbi Autocrine/paracrine activation of the GABA(A) receptor inhibits the proliferation of neurogenic polysialylated neural cell adhesion molecule-positive (PSA-NCAM+) precursor cells from postnatal striatum
    Laurent Nguyen
    Center for Cellular and Molecular Neurobiology, University of Liege, B 4020 Liege, Belgium
    J Neurosci 23:3278-94. 2003
    ..This demonstration of GABA synthesis and GABA(A)R function in striatal PSA-NCAM+ cells may shed new light on the understanding of key extrinsic cues that regulate the developmental potential of postnatal neuronal precursors in the CNS...
  89. ncbi Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuron networks by homogenizing firing rates
    Imre Vida
    Anatomisches Institut, Universitat Freiburg, Albertstr 17, D 79104 Freiburg, Germany
    Neuron 49:107-17. 2006
    ..Thus, shunting inhibition may confer increased robustness to gamma oscillations in the brain...
  90. ncbi Association of GABA(A) receptors and alcohol dependence and the effects of genetic imprinting
    Jiuzhou Song
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202 5122, USA
    Am J Med Genet B Neuropsychiatr Genet 117:39-45. 2003
    ..Maternal transmissions provided no evidence for association. These data are consistent with an association between the expressed alleles in the GABA(A)-gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting...
  91. ncbi Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers
    S L de Haas
    Centre for Human Drug Research, Leiden, The Netherlands
    J Psychopharmacol 21:374-83. 2007
    ..Contrary to lorazepam, TPA023 caused no detectable memory impairment or postural imbalance. These differences reflect the selectivity of TPA023 for different GABA(A) receptor subtypes...
  92. ncbi In vitro networks: cortical mechanisms of anaesthetic action
    B Antkowiak
    Department of Anaesthesiology, University of Tubingen, Max Planck Institute for Biological Cybernetics, Tubingen, Germany
    Br J Anaesth 89:102-11. 2002
  93. ncbi Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of gamma-aminobutyric acid type A receptor alpha1 subunit knockout mice
    Jason E Kralic
    Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
    J Comp Neurol 495:408-21. 2006
    ..In addition, clustering of gephyrin at synaptic sites in cerebellum and thalamus appears to be dependent on expression of a GABA(A) receptor subtype localized postsynaptically...
  94. ncbi Thermodynamic regulation of NKCC1-mediated Cl- cotransport underlies plasticity of GABA(A) signaling in neonatal neurons
    Audrey C Brumback
    Neuroscience Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Neurosci 28:1301-12. 2008
    ..Activity-induced changes in Na+-K+-ATPase activity comprise a novel mechanism for persistent alterations in synaptic signaling mediated by GABA...
  95. ncbi Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition
    F Pouille
    Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
    Science 293:1159-63. 2001
    ..Thus, the subcellular partitioning of feed-forward inhibition enforces precise coincidence detection in the soma, while allowing dendrites to sum incoming activity over broader time windows...
  96. ncbi Synaptogenesis in the cerebellar cortex: differential regulation of gephyrin and GABAA receptors at somatic and dendritic synapses of Purkinje cells
    Laura Viltono
    Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, I 10126 Torino, Italy
    J Comp Neurol 508:579-91. 2008
    ....
  97. ncbi GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts
    Dietmar Benke
    Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Neuropharmacology 56:174-81. 2009
    ..In beta3 (N265M) point-mutated mice the anxiolytic activity of valerenic acid was absent. Thus, neurons expressing beta3 containing GABA(A) receptors are a major cellular substrate for the anxiolytic action of valerian extracts...
  98. ncbi Peripheral benzodiazepine receptors and mitochondrial function
    Pierre Casellas
    Department of Immunology Oncology, Sanofi Synthelabo, Montpellier, France
    Neurochem Int 40:475-86. 2002
    ....
  99. ncbi Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network
    Joël Chavas
    Laboratoire de Physiologie Cérébrale, Universite Paris 5, 75270 Paris, France
    J Neurosci 23:2019-31. 2003
    ..We suggest that the coexistence of excitatory and inhibitory GABA synapses could either buffer the mean firing rate of the interneuron network or introduce different types of correlation between neighboring interneurons, or both...
  100. ncbi L-655,708 enhances cognition in rats but is not proconvulsant at a dose selective for alpha5-containing GABAA receptors
    John R Atack
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Neuropharmacology 51:1023-9. 2006
    ..These data further support the potential of alpha5-containing GABA(A) receptors as a target for novel cognition enhancing drugs...
  101. ncbi Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABA(A) receptors clustered at neocortical synapses
    Valerie Kilman
    Department of Biology and Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA
    J Neurosci 22:1328-37. 2002
    ..Because excitatory and inhibitory synaptic currents are regulated in opposite directions by activity blockade, these data suggest that the balance between excitation and inhibition is dynamically regulated by ongoing activity...

Research Grants72

  1. Efficacy of GABAA a5 receptor inverse agonists in learning impaired rats
    EARL MICHAEL GIBBS; Fiscal Year: 2010
    ..Patients with learning disorders and those suffering from complications due to neurodegenerative diseases will greatly benefit as PWZ-029 moves another step closer to the clinic. ..
  2. GABA chaperoning of epilepsy-associated GABAA receptor mutants.
    Nancy J Leidenheimer; Fiscal Year: 2012
    ..The proposed research investigates a possible mechanism for aiding the correct synthesis of these mutant receptors. Thus, these studies have relevance to the treatment of epilepsy. ..
  3. Neuroplasticity with alcohol dependence
    Scott C Steffensen; Fiscal Year: 2013
    ....
  4. CODING IN AUDITORY NEURONS: EFFECTS OF AMINO ACIDS
    Donald M Caspary; Fiscal Year: 2013
    ..It is hoped that these studies could eventually result in the development of selective new drugs to improve speech understanding in a subset of elderly individuals. ..
  5. Estrogen and TMJ Pain
    Phillip R Kramer; Fiscal Year: 2013
    ..We also expect to determine the mechanism by which estrogen modulates expression of these genes in TG cells. ..
  6. Variations in Hormones During Menopause: Effects on Cognitive and Brain Aging
    Heather A Bimonte-Nelson; Fiscal Year: 2013
    ..This work will yield insight into cognitive effects of the menopause transition, variations in menopause type and HTs, and related mechanisms. ..
  7. Functional Anatomy of REM Sleep: Brainstem-Control
    Gerald A Marks; Fiscal Year: 2013
    ..This research proposal hopes to contribute to our knowledge on the role of REM sleep mechanisms in the etiology and reinforcement of these disorders. ..
  8. Structural Rearrangements in GABA-A Receptors
    CYNTHIA M CZAJKOWSKI; Fiscal Year: 2012
    ....
  9. General Anesthetic Sites in GABA-A Receptor Subunit Interfacial Pockets
    Stuart A Forman; Fiscal Year: 2013
    ....
  10. Hyperpolarized 129-Xenon-based MRI Probes for Brain Injury
    JEREMY PHILLIP CELVER; Fiscal Year: 2010
    ....
  11. CELL BIOLOGY OF THE NEURONAL SODIUM CHANNEL
    William A Catterall; Fiscal Year: 2013
    ..We will examine new-generation, subtype-selective GABA-A receptor activators and test effectiveness of these therapies approaches to control seizures and co-morbidities in DS mice. ..
  12. GABA-A Receptor Pharmacology of Neural Coding in Hippocampal Place Cells
    TARA MONIQUE STEWART; Fiscal Year: 2012
    ..abstract_text> ..
  13. GABA-active neurosteroids in contextual fear responses
    Graziano Pinna; Fiscal Year: 2011
    ....
  14. GABA channels and dopamine in striatum
    Stefano Vicini; Fiscal Year: 2013
    ....
  15. Presynaptic GABA-A receptor activation in auditory brainstem axon terminals
    CATHERINE JEANNE CHALENSKI WEISZ; Fiscal Year: 2013
    ..A full understanding of the complexity of the perception of sound will guide refined therapies for treatment of hearing disorders. ..
  16. Molecular Regulation of GABA(A) Receptor Function in Amygdala
    Kerry J Ressler; Fiscal Year: 2010
    ..Understanding the mechanisms shared by stress and drug response is critical for understanding pathophysiology and proposing new treatments for these highly comorbid disorders. ..
  17. Systems Biology for Studies of Cognition in Down Syndrome
    Katheleen Gardiner; Fiscal Year: 2012
    ..The goal is to define key abnormalities in pathways critical for learning and memory and to identify effective targets for development of potential therapeutics. ..
  18. Novel actions of neurosteroids on GABA (A) receptor trafficking
    Stephen J Moss; Fiscal Year: 2013
    ..Moreover such information is likely to lead to the development of more efficacious treatments for anxiety, depression, premenstrual syndrome, schizophrenia and substance abuse. ..
  19. Suprachiasmatic Nucleus Output Pathway for Learning and Memory
    H Craig Heller; Fiscal Year: 2013
    ..Thus, a major benefit of this proposal is that the results will lead to a much needed animal model in which we can study circadian contributions to human pathologies that are of interest to clinicians. ..
  20. GABAA Receptor-Interacting Proteins
    Angel L De Blas; Fiscal Year: 2013
    ....
  21. Chronic nicotine: cell-specific receptor and circuit alterations in basal ganglia
    Henry A Lester; Fiscal Year: 2013
    ..between smoking and Parkinson's disease. Understanding the cellular and circuit changes induced by chronic nicotine in basal ganglia could lead to new therapies. ..
  22. Personalized Treatment with Pharmacotherapy and CBT for Moderate Problem Drinking
    Andrew C Chen; Fiscal Year: 2013
    ....
  23. GABA(A) Receptor Subunit Regulation in Epileptogenesis
    Shelley J Russek; Fiscal Year: 2013
    ..The proposed studies seek to find new ways of treating and preventing epilepsy by identifying and then reversing the changes in brain cells that lead to this condition. ..
  24. Role of Benzodiazepine Receptor in Leydig Cell Function
    Vassilios Papadopoulos; Fiscal Year: 2011
    ....
  25. GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
    Nancy A Ator; Fiscal Year: 2011
    ....
  26. IMMATURE HIPPOCAMPUS: EPILEPTOGENIC PROPERTIES
    JOHN WILLIAM SWANN; Fiscal Year: 2012
    ..Results suggest that developing neurons grow abnormally slow after seizures. We are studying why this happens so therapies can be developed to prevent learning disabilities. ..
  27. Structure of the GABA-A Receptor Binding Sites
    CYNTHIA M CZAJKOWSKI; Fiscal Year: 2013
    ....
  28. Rational polytherapy in the treatment of cholinergic seizures
    Claude G Wasterlain; Fiscal Year: 2013
    ....
  29. Structural and Functional Alterations of Interneurons in Models of Schizophrenia
    Istvan Mody; Fiscal Year: 2012
    ..The rational design of GABAergic therapeutics, though, will require a more detailed understanding of how functional imbalances in the multiple facets of GABAA receptor-mediated signaling contribute to schizophrenic symptoms. ..
  30. Structure of the GABA-A Receptor Binding Sites
    CYNTHIA M CZAJKOWSKI; Fiscal Year: 2012
    ..abstract_text> ..
  31. Chemical Profiles of Brain Synapses at Ages Vulnerable to Activity-Based Anorexia
    Nicole C Barbarich-Marsteller; Fiscal Year: 2011
    ..The results obtained from this study will provide the rationale for exploring a new pharmacologic treatment that targets the site of action of THP upon the GABAergic system within limbic pathways. ..
  32. Use of a mouse model of anxious depression to assess the safety of pediatric anti
    Bernhard Luscher; Fiscal Year: 2010
    ..In addition, they may advance the design and safety of antidepressant and anxiolytic therapies directed specifically at pediatric and adolescent patients. ..
  33. The Regulation of GABAA Receptor Cell Surface Stability
    Stephen Moss; Fiscal Year: 2009
    ..abstract_text> ..
  34. Neurosteroid Modulation of Extrasynaptic GABAA Receptors
    EYDITH JANICE COMENENCIA ORTIZ; Fiscal Year: 2012
    ..The studies in this application will provide insight into neurosteroid-mediated alterations in neuronal excitability an might contribute to the development of novel treatments for postpartum depression, epilepsy and anxiety disorders. ..
  35. GABAA subtype-specific pharmacological modulation of reward-related behavior
    Uwe Rudolph; Fiscal Year: 2010
    ....
  36. GABA(A) Receptor Assembly/Trafficking/Function and Epilepsy Missense Mutations
    ROBERT LOUDEN MACDONALD; Fiscal Year: 2013
    ..In Specific Aim 3 we will characterize the effects of the rare nsSNPs found in non hEP genes only in cases or in hEP genes on functional properties and/or biogenesis of GABAARs. ..
  37. GABA(A) RECEPTOR TRAFFICKING AND EPILEPTOGENESIS
    Marco I Gonzalez; Fiscal Year: 2013
    ..The proposed studies aim to develop a better understanding of the molecular mechanisms that trigger epilepsy development to provide new therapeutic targets and generate novel strategies to ameliorate epilepsy progression. ..
  38. Prenatal ethanol exposure, arousal and the Sudden Infant Death Syndrome (SIDS)
    Robert A Darnall; Fiscal Year: 2013
    ....
  39. GABA Receptors and Hilar Neuron Survival in Epilepsy
    Carolyn R Houser; Fiscal Year: 2013
    ..By allowing selective manipulation of hilar neurons in the intact brain, these studies will provide unique views of their function within normal and altered neuronal circuits. ..
  40. Efficacy of flupirtine for treatment of neonatal hypoxic-ischemic encephalopathy
    Yogendra H Raol; Fiscal Year: 2013
    ..These studies will determine if flupirtine effectively treats HI without adversely affecting development. If successful, these studies should rapidly translate into new effective treatment for neonatal HI. ..
  41. Effects of Ethanol TNF Induced Cytotoxicity
    John G Pastorino; Fiscal Year: 2012
    ..Moreover these effects of ethanol can be ameliorated by activation of AMPK. ..
  42. A Neurosteroid-based Novel Treatment for OP-Intoxication
    Doodipala Samba Reddy; Fiscal Year: 2012
    ..Therefore, the outcome of this research will set the stage for rapid development of neurosteroids as effective countermeasures against chemical threats. ..
  43. The role of ubiquitination in regulating GABA(A) receptor functional expression
    Stephen J Moss; Fiscal Year: 2010
    ....
  44. Molecular Determinants of GABAA Receptor Gene Regulation
    SHELLEY JUNE RUSSEK; Fiscal Year: 2010
    ..Using viral-mediated delivery of RNAi to target both endogenous Egr3 and GABRA4 gene expression, we will test whether increased alpha-4 subunits are required for development of spontaneous seizures in TLE rats. ..
  45. Sim1 Neurons and Body Weight Regulation
    Qingchun Tong; Fiscal Year: 2013
    ....
  46. Multiple circadian oscillators: Regulation of a neuroendocrine rhythm
    Sandra J Legan; Fiscal Year: 2012
    ....
  47. AGE RELATED SEIZURE SUPPRESSION
    Solomon L Moshe; Fiscal Year: 2011
    ....
  48. Ethanol discrimination in aged female monkeys
    Christa M Helms; Fiscal Year: 2010
    ....
  49. GABAergic Mechanisms of Comorbid Alcohol and Nicotine Dependence
    Kelly P Cosgrove; Fiscal Year: 2013
    ..These studies will ultimately provide information on how to more successfully treat these costly addictions. ..
  50. Neuroactive Steroid GABAA Receptor Positive Modulators for Fragile X Syndrome
    Albert J Robichaud; Fiscal Year: 2013
    ..The Blueprint for Neurotherapeutics can facilitate the realization of this goal through partnership with SAGE Therapeutics. ..
  51. Structural investigation of a GABA receptor subtype
    DEREK CLAXTON; Fiscal Year: 2013
    ..The results of this work will substantially contribute to the understanding of GABAA receptor structure and the allosteric effects of ligand binding on channel behavior. ..
  52. Proneurotrophin signaling in epilepsy
    AJAY THOMAS; Fiscal Year: 2013
    ....
  53. Early Life Seizures and Development of Gabaergic Inhibition in the Human Brain
    Laura A Jansen; Fiscal Year: 2013
    ..Information gained as a result of this study could have direct clinical applications that produce improved medical and neurologic care of infants and neonates. ..
  54. Synaptic Regulation of Neurogenesis in the Dentate Gyrus
    Brian E Derrick; Fiscal Year: 2012
    ..abstract_text> ..
  55. Does Anesthetic Solubility Determine Receptor Specificity?
    ROBERT JOSEPH BROSNAN; Fiscal Year: 2013
    ..The role of water solubility as a determinant of drug-receptor modulation would also add additional support to theories of anesthetic action at aqueous interfacial sites around cell receptor proteins. ..
  56. Design of New Therapeutic Agents to Treat Schizophrenia
    James M Cook; Fiscal Year: 2013
    ..The proposed work is significant because it represents the first step in a continuum of research to develop the first therapies for impaired cognitive function and negative symptoms of schizophrenia patients. ..
  57. Tonic Inhibition in Thalamocortical Network Function and Absence Epilepsy
    Mathew V Jones; Fiscal Year: 2013
    ..synaptically driven excitability? AIM 2 - How does tonic inhibition regulate the functional connectivity of the thalamocortical network? AIM 3 - How does tonic inhibition regulate behavioral states, including absence seizures and sleep? ..
  58. PKC Delta in Ethanol Regulation of GABA-A Receptors and Behavior
    Robert O Messing; Fiscal Year: 2013
    ..abstract_text> ..
  59. The role of GABA-mimetic metabolites in neurodevelopmental and neuropsychiatric d
    Joseph A Gogos; Fiscal Year: 2013
    ..These results will also lay the foundation for guiding future studies targeted at the development of pharmacological rescue strategies for these diseases. ..
  60. NEUROSTEROID MODULATION OF ETHANOL WITHDRAWAL SEVERITY
    David J Rossi; Fiscal Year: 2013
    ..Thus, the proposed experiments will establish the importance of altered hippocampal neurosteroid composition and GABAA receptor pharmacology in mediating ethanol withdrawal severity. ..
  61. Neurochemical Bases for the Rewarding Effects of Ethanol
    Patricia H Janak; Fiscal Year: 2012
    ....
  62. Interactions between neuronal networks that regulate food intake and body weight
    Lori M Zeltser; Fiscal Year: 2013
    ....
  63. ANESTHETIC MECHANISMS AND GABA-A RECEPTOR STRUCTURE
    MYLES AKABAS; Fiscal Year: 2001
    ..It will also provide insights into the conformational changes induced by agonist and drug binding and thereby provide an understanding of anesthetic action at a molecular level. ..
  64. FUNCTIONAL ANALYSIS OF NOVEL GABA RECEPTOR IN DROSOPHILA
    Richard ffrench Constant; Fiscal Year: 1999
    ....
  65. BENZODIAZEPINES AND THE GABA A RECEPTOR
    JOSEPH NEALE; Fiscal Year: 1999
    ....
  66. Propofol Interactions with GABA-A Receptors
    MYLES AKABAS; Fiscal Year: 2009
    ..They may provide a rational basis for design of new, safer general anesthetics. ..
  67. HEPATIC COMA--GLIAL BENZODIAZEPINE RECEPTORS & STEROIDS
    Michael Norenberg; Fiscal Year: 2000
    ....
  68. OXYTOCIN REGULATION BY NEUROSTEROIDS & GABA-A RECEPTOR
    Janet Amico; Fiscal Year: 2003
    ..c.v. to the steroid-treated ovariectomized rat or the pregnant rat and measure indices of maternal behavior and levels of hypothalamic OT mRNA and OT peptide. ..
  69. GABAA RECEPTOR BETA-SUBUNIT AND GENERAL ANESTHETICS
    Jay Yang; Fiscal Year: 2002
    ..The experiments proposed will add quantitative and mechanistic information to general anesthetic molecular pharmacology and move this field of investigation closer towards truly understanding how these clinically essential drugs work. ..
  70. STEROID REGULATION OF ION CHANNELS
    Leslie Henderson; Fiscal Year: 1999
    ....
  71. GABA-A receptor plasticity: regulation by hypoxia
    RUTH SIEGEL; Fiscal Year: 2009
    ..Identifying the molecular machinery involved in the response to hypoxia is an essential first step for creating novel therapeutic approaches to combat a variety of potentially life-threatening situations. ..
  72. Non-sedating modulators of GABA-A receptors for anxiety
    KELVIN GEE; Fiscal Year: 2009
    ..The focus of the proposed project is to develop therapeutics to bolster the shortfall of therapies for the treatment of anxiety disorders, an underserved therapeutic area that affects 3.1% of the general population over 18. ..