Neil L Harrison

Summary

Affiliation: Cornell University
Country: USA

Publications

  1. pmc Ethanol modulates synaptic and extrasynaptic GABAA receptors in the thalamus
    Fan Jia
    Department of Anesthesiology, C V Starr Laboratory for Molecular Neuropharmacology, Weill Cornell Medical College, New York, New York 10065, USA
    J Pharmacol Exp Ther 326:475-82. 2008
  2. doi request reprint Sensitization of nociceptive ion channels by inhaled anesthetics--a pain in the gas?
    Neil Harrison
    Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA
    Mol Pharmacol 74:1180-2. 2008
  3. ncbi request reprint Mechanisms of sleep induction by GABA(A) receptor agonists
    Neil L Harrison
    Weill Medical College of Cornell University, New York, NY 10021, USA
    J Clin Psychiatry 68:6-12. 2007
  4. doi request reprint Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus
    Fan Jia
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10065 4897, USA
    J Neurosci 28:106-15. 2008
  5. pmc Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms
    Shui Wang Ying
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A 1050, New York, NY 10065, United States
    Neuropharmacology 56:438-47. 2009
  6. ncbi request reprint 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
  7. ncbi request reprint Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons
    Shui Wang Ying
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Eur J Neurosci 23:465-80. 2006
  8. pmc Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors
    Angelo Keramidas
    CV Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, NY, NY 10021, USA
    J Gen Physiol 131:163-81. 2008
  9. ncbi request reprint Transmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit
    Claude M Schofield
    Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA
    Brain Res 1032:30-5. 2005
  10. ncbi request reprint Isoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the thalamus
    Fan Jia
    Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A 1050, New York, NY 10065, USA
    J Pharmacol Exp Ther 324:1127-35. 2008

Research Grants

  1. Alcohol and GABA in the Thalamus
    Neil Harrison; Fiscal Year: 2007

Collaborators

Detail Information

Publications46

  1. pmc Ethanol modulates synaptic and extrasynaptic GABAA receptors in the thalamus
    Fan Jia
    Department of Anesthesiology, C V Starr Laboratory for Molecular Neuropharmacology, Weill Cornell Medical College, New York, New York 10065, USA
    J Pharmacol Exp Ther 326:475-82. 2008
    ....
  2. doi request reprint Sensitization of nociceptive ion channels by inhaled anesthetics--a pain in the gas?
    Neil Harrison
    Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA
    Mol Pharmacol 74:1180-2. 2008
    ..This finding provides another example of an ion channel in which the anesthetic acts to modify channel gating. This may have important clinical implications in view of the role of TRPV1 in nociception...
  3. ncbi request reprint Mechanisms of sleep induction by GABA(A) receptor agonists
    Neil L Harrison
    Weill Medical College of Cornell University, New York, NY 10021, USA
    J Clin Psychiatry 68:6-12. 2007
    ..This review will examine the role of heterogeneity of GABA(A) receptors, and recent research demonstrating subunit-dependent modulation of receptors by novel pharmacologic agents will be discussed...
  4. doi request reprint Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus
    Fan Jia
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10065 4897, USA
    J Neurosci 28:106-15. 2008
    ..We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA(A)-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus...
  5. pmc Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms
    Shui Wang Ying
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A 1050, New York, NY 10065, United States
    Neuropharmacology 56:438-47. 2009
    ..We conclude that isoflurane enhances inhibition of thalamic neurons in VB via GABA(A)-R-dependent, but in RTN via GABA(A)-R-independent, mechanisms...
  6. ncbi request reprint 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...
  7. ncbi request reprint Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons
    Shui Wang Ying
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Eur J Neurosci 23:465-80. 2006
    ..These results suggest that suppression of I(h) may contribute to the inhibition of thalamocortical activity during propofol anesthesia. Longer-term effects represent a novel form of propofol-mediated regulation of I(h)...
  8. pmc Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors
    Angelo Keramidas
    CV Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, NY, NY 10021, USA
    J Gen Physiol 131:163-81. 2008
    ..Our data identify kinetic properties that are receptor-subtype specific and others that are agonist specific, including unitary conductance...
  9. ncbi request reprint Transmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit
    Claude M Schofield
    Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA
    Brain Res 1032:30-5. 2005
    ..These findings are consistent with the action of isoflurane on a critical site within the transmembrane domains of the receptor and suggest a degree of functional homology between the GABA(A) alpha-1, -2, and -3 subunits...
  10. ncbi request reprint Isoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the thalamus
    Fan Jia
    Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A 1050, New York, NY 10065, USA
    J Pharmacol Exp Ther 324:1127-35. 2008
    ....
  11. ncbi request reprint Alanine-scanning mutagenesis in the signature disulfide loop of the glycine receptor alpha 1 subunit: critical residues for activation and modulation
    Claude M Schofield
    Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA
    Biochemistry 43:10058-63. 2004
    ..The present data implicate the Cys loop as an important functional moiety in the process of glycine receptor activation and allosteric regulation by anesthetics...
  12. ncbi request reprint GABA(A)-R alpha1 subunit knockin mutation leads to abnormal EEG and anesthetic-induced seizure-like activity in mice
    Frank P Elsen
    Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Brain Res 1078:60-70. 2006
    ....
  13. doi request reprint The modulation of synaptic GABA(A) receptors in the thalamus by eszopiclone and zolpidem
    Fan Jia
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, NewYork, New York 10065, USA
    J Pharmacol Exp Ther 328:1000-6. 2009
    ..This distinct pattern of activity on thalamic neurons may contribute to some of the observed differences in the clinical effects of these two hypnotics...
  14. pmc The pre-M1 segment of the alpha1 subunit is a transduction element in the activation of the GABAA receptor
    Angelo Keramidas
    CV Starr Laboratory for Molecular Pharmacology, Department of Anesthesiology, Weill Medical College, Cornell University, A 1040, 1300 York Avenue, New York, NY 10021, USA
    J Physiol 575:11-22. 2006
    ..77 mM GABA in WT and 1.4 mM GABA in the alpha1(K220A)beta2gamma2s channels. The beta-10 strand (pre-M1 segment) emerges, from this and other studies, as a key functional component in the activation of the GABAAR...
  15. ncbi request reprint Impairment of hyperpolarization-activated, cyclic nucleotide-gated channel function by the intravenous general anesthetic propofol
    Luisa P Cacheaux
    CV Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College, Cornell University, New York, NY 10021, USA
    J Pharmacol Exp Ther 315:517-25. 2005
    ....
  16. ncbi request reprint Charged residues in the beta2 subunit involved in GABAA receptor activation
    Thomas L Kash
    Graduate Program in Neuroscience, Weill Graduate School of Biomedical Sciences, Cornell University, New York, NY 10021, USA
    J Biol Chem 279:4887-93. 2004
    ..The results suggest that interactions between an acidic residue in loop 7 (Asp146) and a basic residue in pre-transmembrane domain-1 (Lys215) are involved in coupling agonist binding to channel gating...
  17. ncbi request reprint Effects of isoflurane on gamma-aminobutyric acid type A receptors activated by full and partial agonists
    Norbert Topf
    Department of Anesthesiology, Weill Medical College of Cornell University, New York, New York 10021, USA
    Anesthesiology 98:306-11. 2003
    ..They then compared the effects of clinically relevant concentrations of isoflurane on the actions of GABA and piperidine-4-sulfonic acid (P4S), a partial agonist at the GABA(A) receptor...
  18. pmc Derivation of midbrain dopamine neurons from human embryonic stem cells
    Anselme L Perrier
    Laboratory of Stem Cell and Tumor Biology, Division of Neurosurgery and Developmental Biology Program, and Cell Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 101:12543-8. 2004
    ..This experimental system also provides a powerful tool to probe the molecular mechanisms that control the development and function of human midbrain DA neurons...
  19. ncbi request reprint Evaluation of a proposed mechanism of ligand-gated ion channel activation in the GABAA and glycine receptors
    Thomas L Kash
    Graduate Program in Neuroscience, Weill Graduate School of Biomedical Sciences, Cornell University, New York, NY 10021, USA
    Neurosci Lett 371:230-4. 2004
    ..This conclusion is consistent with other recent reports in which mutations of residues distributed throughout several loops of nAChR, GABA(A) and glycine receptors had large effects on gating behavior...
  20. pmc Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive alpha1 GABA A receptors
    David F Werner
    Departments of Anesthesiology and Pharmacology, Weill Medical College of Cornell University, New York, NY, USA
    Alcohol Clin Exp Res 33:289-99. 2009
    ..The alpha1 GABA(A)-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that alpha1-GABA(A)-Rs mediate in part these effects of ethanol...
  21. ncbi request reprint Alcohol regulates gene expression in neurons via activation of heat shock factor 1
    Leonardo Pignataro
    Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10021, USA
    J Neurosci 27:12957-66. 2007
    ....
  22. ncbi request reprint A highly conserved aspartic acid residue in the signature disulfide loop of the alpha 1 subunit is a determinant of gating in the glycine receptor
    Claude M Schofield
    Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 278:34079-83. 2003
    ..This finding adds to an emerging body of evidence supporting the involvement of the Cys loop in the gating mechanism of the LGICs...
  23. ncbi request reprint Coupling of agonist binding to channel gating in the GABA(A) receptor
    Thomas L Kash
    Graduate Program in Neuroscience, Weill Graduate School of Biomedical Sciences, Cornell University, New York, New York 10021, USA
    Nature 421:272-5. 2003
    ..During gating, Asp 149 and Lys 279 seem to move closer to one another, providing a potential mechanism for the coupling of ligand binding to opening of the ion channel...
  24. ncbi request reprint GABAA receptors in the thalamus: alpha4 subunit expression and alcohol sensitivity
    Fan Jia
    Department of Anesthesiology, Weill Medical College, Cornell University, New York, NY 10021, USA
    Alcohol 41:177-85. 2007
    ..Investigating the effects of alcohol on both synaptic and extrasynaptic GABAA-Rs in the thalamus should help us to understand the mechanisms underlying the interaction between alcohol and sleep...
  25. pmc The regulation of neuronal gene expression by alcohol
    Leonardo Pignataro
    Department of Anesthesiology and Department of Pharmacology, The College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Pharmacol Ther 124:324-35. 2009
    ..In this review we will describe some of the most interesting cellular and microarray work in the field, and will outline specific examples of genes for which the mechanisms of regulation by alcohol are now somewhat understood...
  26. pmc The activation mechanism of alpha1beta2gamma2S and alpha3beta3gamma2S GABAA receptors
    Angelo Keramidas
    Department of Anesthesiology, Columbia University, New York, NY 10032, USA
    J Gen Physiol 135:59-75. 2010
    ....
  27. ncbi request reprint Transcriptional regulation of the mouse gene encoding the alpha-4 subunit of the GABAA receptor
    Limei Ma
    Department of Anesthesiology, Weill Medical College, Cornell University, New York, New York 10021, USA
    J Biol Chem 279:40451-61. 2004
    ..Both Sp3 and Sp4 transcription factors can interact with the two Sp1 binding sites within the minimal promoter and are critical for maximal activity of the promoter in neurons...
  28. ncbi request reprint Emerging molecular mechanisms of general anesthetic action
    Hugh C Hemmings
    Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, 1300 York Avenue, Box 50, New York, NY 10021, USA
    Trends Pharmacol Sci 26:503-10. 2005
    ..In this article, these developments, which have important implications for the development of more-selective anesthetics, are reviewed in the context of recent advances in ion channel structure and function...
  29. ncbi request reprint Hemoglobin metabolites mimic benzodiazepines and are possible mediators of hepatic encephalopathy
    Brian J Ruscito
    Graduate Program in Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA
    Blood 102:1525-8. 2003
    ..The accumulation of these porphyrins under pathophysiologic conditions provides a potentially novel mechanism for the central manifestations of HE...
  30. ncbi request reprint Molecular volume determines the activity of the halogenated alkane bromoform at wild-type and mutant GABA(A) receptors
    Thomas L Kash
    Graduate Program in Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA
    Brain Res 960:36-41. 2003
    ..The molecular volume of bromoform is closest to that of halothane, and therefore our data are consistent with the idea that molecular volume is an important determinant of inhaled anesthetic activity at the GABA(A) receptor...
  31. pmc Anesthetics interfere with axon guidance in developing mouse neocortical neurons in vitro via a γ-aminobutyric acid type A receptor mechanism
    C David Mintz
    Department of Anesthesiology, Columbia University, New York, New York 10032, USA
    Anesthesiology 118:825-33. 2013
    ..The generation of neuronal circuits, a complex process in which axons follow guidance cues to dendritic targets, is an unexplored potential target for this type of toxicity...
  32. pmc Striatal D2 receptors regulate dendritic morphology of medium spiny neurons via Kir2 channels
    Maxime Cazorla
    Department of Psychiatry, Pharmacology, and Anesthesiology, Columbia University, New York, New York 10032, USA
    J Neurosci 32:2398-409. 2012
    ....
  33. ncbi request reprint Prolongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABA(A) receptor alpha1 subunit
    Peter A Goldstein
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College, Cornell University, New York, New York 10021, USA
    J Neurophysiol 88:3208-17. 2002
    ....
  34. ncbi request reprint Tryptophan scanning mutagenesis in TM4 of the GABA(A) receptor alpha1 subunit: implications for modulation by inhaled anesthetics and ion channel structure
    Andrew Jenkins
    Department of Anesthesiology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Neuropharmacology 43:669-78. 2002
    ..These data are consistent with a role for these residues at the extracellular end of TM4 in anesthetic modulation of GABA(A) receptors...
  35. ncbi request reprint Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice
    Tiziano Barberi
    Laboratory of Stem Cell and Tumor Biology, Division of Neurosurgery and Developmental Biology Program, Weill Medical College of Cornell University, New York, New York 10021, USA
    Nat Biotechnol 21:1200-7. 2003
    ..Furthermore, transplantation of ES and ntES cell-derived dopaminergic neurons corrected the phenotype of a mouse model of Parkinson disease, demonstrating an in vivo application of therapeutic cloning in neural disease...
  36. ncbi request reprint Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane
    James M Sonner
    Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143 0464, USA
    Anesthesiology 106:107-13. 2007
    ..To test this, the authors created gene knock-in mice harboring mutations that render the receptors insensitive to isoflurane while preserving sensitivity to halothane...
  37. ncbi request reprint General anesthesia research: aroused from a deep sleep?
    Neil L Harrison
    Nat Neurosci 5:928-9. 2002
  38. pmc 4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA(A) receptor
    Matthew D Krasowski
    Department of Anesthesia and Critical Care, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    J Med Chem 45:3210-21. 2002
    ....
  39. ncbi request reprint 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...
  40. ncbi request reprint The effects of isoflurane on desensitized wild-type and alpha 1(S270H) gamma-aminobutyric acid type A receptors
    Adam C Hall
    Department of Biological Sciences, Neuroscience Program, Smith College, Northampton, Massachusetts 01063, USA
    Anesth Analg 98:1297-304, table of contents. 2004
    ..The effects of isoflurane on desensitized receptors may be partly responsible for the prolongation of IPSCs during anesthesia...
  41. ncbi request reprint Subunit-dependent block by isoflurane of wild-type and mutant alpha(1)S270H GABA(A) receptor currents in Xenopus oocytes
    Adam C Hall
    Neuroscience and Biochemistry Programs, Department of Biological Sciences, Clark Science Center, Smith College, Northampton, MA 01063, USA
    Neurosci Lett 382:332-7. 2005
    ..In conclusion, isoflurane binds with low affinity and with subunit-specificity to an inhibitory site on the GABA(A) receptor that is distinct from the site that facilitates positive modulation at the extracellular end of the pore...
  42. pmc Normal acute behavioral responses to moderate/high dose ethanol in GABAA receptor alpha 4 subunit knockout mice
    Dev Chandra
    Departments of Anesthesiology and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Alcohol Clin Exp Res 32:10-8. 2008
    ..We therefore hypothesized that those behavioral responses to EtOH that are mediated by alpha 4-containing GABA(A)-Rs would be diminished in alpha 4 knockout mice...
  43. ncbi request reprint Knockin mice with ethanol-insensitive alpha1-containing gamma-aminobutyric acid type A receptors display selective alterations in behavioral responses to ethanol
    David F Werner
    Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    J Pharmacol Exp Ther 319:219-27. 2006
    ..Overall, these studies demonstrate that the postsynaptic effects of ethanol at GABAergic synapses containing the alpha1 subunit are important for specific ethanol-induced behavioral effects...
  44. doi request reprint Molecular modeling and mutagenesis reveals a tetradentate binding site for Zn2+ in GABA(A) alphabeta receptors and provides a structural basis for the modulating effect of the gamma subunit
    James R Trudell
    Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305 5117, USA
    J Chem Inf Model 48:344-9. 2008
    ..Sensitivity to Zn2+ was restored in the double mutant receptor, alpha1beta2gamma2 (I282H; K285E), in which the competition with lysine was removed and a more favorable Zn2+ binding site was formed...
  45. ncbi request reprint Knockin' on the door of general anesthetic mechanisms: but will U.S. researchers be shut out?
    Neil L Harrison
    Anesth Analg 97:616-8. 2003
  46. ncbi request reprint A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor alpha1 subunit reduces membrane expression and impairs gating by agonists
    Pasqualina Castaldo
    Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
    J Biol Chem 279:25598-604. 2004
    ..In conclusion, multiple mechanisms may explain the dramatic decrease in GlyR function caused by the R218Q mutation, possibly providing the molecular basis for its association with a more severe clinical phenotype...

Research Grants2

  1. Alcohol and GABA in the Thalamus
    Neil Harrison; Fiscal Year: 2007
    ....