Extrasynaptic GABAA receptors in the brainstem and spinal cord: Structure and function

Current Pharmaceutical Design

Volumn 19, Issue 24, 2013, Pages 4485-4497

  Delgado Lezama, Rodolfo ^a   Loeza Alcocer, Emanuel ^a   Andrés, Carmen ^a   Aguilar, Justo ^a   Guertin, Pierre A ^b   Felix, Ricardo ^a  

^a DEPARTAMENTO DE FÍSICA   (Mexico)

^b UNIVERSITÉ LAVAL   (Canada)

Author keywords

Extrasynaptic GABAA receptors; GABA; Motoneurons; Primary afferent fibers; Spinal cord

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; RECEPTOR SUBUNIT;

BRAIN STEM; GABAERGIC SYSTEM; MOTONEURON; MOTOR CONTROL; NONHUMAN; OPTIC NERVE; PRIORITY JOURNAL; REVIEW; SPINAL CORD;

AFFERENT PATHWAYS; ANIMALS; BRAIN STEM; EXTRACELLULAR SPACE; HUMANS; MOTOR NEURONS; PROTEIN SUBUNITS; RECEPTORS, GABA-A; REFLEX; SPINAL CORD; SYNAPSES; SYNAPTIC POTENTIALS;

EID: 84878656266     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319240013     Document Type: Review

References (155)

1. Allain AE, Le Corronc H, Delpy A, et al. Maturation of the GABAergic transmission in normal and pathologic motoneurons. Neural Plast [serial on the internet]. 2011 Jul 20; 2011: [about 13 screens]. Available from: http: //www.hindawi.com/journals/np/2011/905624.
2. Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev 2007; 87(4): 1215-84.
3. Kriegstein AR, Owens DF. GABA may act as a self-limiting trophic factor at developing synapses. Sci STKE [serial on the internet]. 2001 Aug 14; 2001(95): [about 4 screens]. Available from: http: //stke.sciencemag.org/cgi/content/full/OC_sigtrans; 2001/95/pe1.
4. Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 2002; 3(9): 715-27.
5. Kaeser GE, Rabe BA, Saha MS. Cloning and characterization of GABAA α subunits and GABAB subunits in Xenopus laevis during development. Dev Dyn 2011; 240(4): 862-73.
6. Ritter B, Zhang W. Early postnatal maturation of GABAAmediated inhibition in the brainstem respiratory rhythm-generating network of the mouse. Eur J Neurosci 2000; 12(8): 2975-84.
7. Singer J, Talley EM, Bayliss DA, Berger AJ. Development of glycinergic synaptic transmission to rat brain stem motoneurons. J Neurophysiol 1998; 80(5): 2608-20.
8. Delpy A, Allain AE, Meyrand P, Branchereau P. NKCC1 cotransporter inactivation underlies embryonic development of chloridemediated inhibition in mouse spinal motoneuron. J Physiol 2008; 586(4): 1059-75.
9. Jean-Xavier C, Mentis GZ, O'Donovan MJ, Cattaert D, Vinay L. Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord. Proc Natl Acad Sci USA 2007; 104(27): 11477-82.
10. Stil A, Liabeuf S, Jean-Xavier C, Brocard C, Viemari JC, Vinay L. Developmental up-regulation of the potassium-chloride cotransporter type 2 in the rat lumbar spinal cord. Neuroscience 2009; 164(2): 809-21.
11. Deschenes M, Feltz P, Lamour Y. A model for an estimate in vivo of the ionic basis of presynaptic inhibition: an intracellular analysis of the GABA-induced depolarization in rat dorsal root ganglia. Brain Res 1976; 118(3): 486-93.
12. Gallagher JP, Higashi H, Nishi S. Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurons. J Physiol 1978; 275: 263-82.
13. Alvarez-Leefmans FJ, Gamiño SM, Giraldez F, Noguerón I. Intracellular chloride regulation in amphibian dorsal root ganglion neurones studied with ion-selective microelectrodes. J Physiol 1988; 406: 225-46.
14. Alvarez-Leefmans FJ, Nani A, Márquez S. Chloride transport, osmotic balance, and presynaptic inhibition. In: Rudomin P, Romo R, Mendell LM. Eds. Presynaptic inhibition and neural control. Oxford University Press, New York 1998; pp. 50-79.
15. Curtis DR, Lodge D, Brand SJ. GABA and spinal afferent terminal excitability in the cat. Brain Res 1977; 130: 360-3.
16. Curtis DR, Gynther BD, Beattie DT, Lacey G. An in vivo electrophysiological investigation of group Ia afferent fibres and ventral horn terminations in the cat spinal cord. Exp Brain Res 1995; 106(3): 403-17.
17. Levy RA. The effect of intravenously administered gammaaminobutyric acid on afferent fiber polarization. Brain Res 1975; 92(1): 21-34.
18. Rudomin P, Engberg I, Jiménez I. Mechanisms involved in presynaptic depolarization of group I and rubrospinal fibers in cat spinal cord. J Neurophysiol 1981; 46(3): 532-48.
19. Willis WD. Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 1999; 124(4): 395-421.
20. Rudomin P, Schmidt RF. Presynaptic inhibition in the vertebrate spinal cord revisited. Exp Brain Res 1999; 129(1): 1-37.
21. Olsen RW, Sieghart W. International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Pharmacol Rev 2008; 60(3): 243-60.
22. Olsen RW, Sieghart W. GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 2009; 56(1): 141-8.
23. Fritschy JM, Weinmann O, Wenzel A, Benke D. Synapse-specific localization of NMDA and GABAA receptor subunits revealed by antigen-retrieval immunohistochemistry. J Comp Neurol 1998; 390: 194-210.
24. Somogyi P, Fritschy JM, Benke D, Roberts JDB, Sieghart W. The gamma 2 subunit of the GABAA-receptor is concentrated in synaptic junctions containing the alpha 1 and beta 2/3 subunits in hippocampus, cerebellum and globus pallidus. Neuropharmacology 1996; 35: 1425-44.
25. Nusser Z, Ahmad Z, Tretter V, et al. Alterations in the expression of GABAA receptor subunits in cerebellar granule cells after the disruption of the alpha6 subunit gene. Eur J Neurosci 1999; 11(5): 1685-97.
26. Nusser Z, Roberts JDB, Baude A, Richards JG, Somogyi P. Relative densities of synaptic and extrasynaptic GABAA receptors on cerebellar granule cells as determined by a quantitative immunogold method. J Neurosci 1995; 15: 2948-60.
27. Nusser Z, Sieghart W, Benke D, Fritschy JM, Somogyi P. Differential synaptic localization of two major gamma-aminobutyric acid type A receptor alpha subunits on hippocampal pyramidal cells. Proc Natl Acad Sci USA 1996; 93(21): 11939-44.
28. Nusser Z, Cull-Candy S, Farrant M. Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. Neuron 1997; 19(3): 697-709.
29. Nusser Z, Sieghart W, Somogyi P. Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J Neurosci 1998; 18(5): 1693-703.
30. Möhler H, Fritschy JM, Rudolph U. A new benzodiazepine pharmacology. J Pharmacol Exp Ther 2002; 300(1): 2-8.
31. Somogyi P, Takagi H, Richards JG, Mohler H. Subcellular Localization of Benzodiazepine/GABA, Receptors in the Cerebellum of Rat, Cat, and Monkey Using Monoclonal Antibodies. J Neurosci 1989; 9(6): 2197-209.
32. Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 2005; 6(3): 215-29.
33. Kullmann DM, Ruiz A, Rusakov DM, Scott R, Semyanov A, Walker MC. Presynaptic, extrasynaptic and axonal GABAA receptors in the CNS: where and why? Prog Biophys Mol Biol 2005; 87: 33-46.
34. Brickley S, Cull-Candy S, Farrant M. Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol 1996; 497: 753-9.
35. Chadderton P, Margrie TW, Hausser M. Integration of quanta in cerebellar granule cells during sensory processing. Nature 2004; 428: 856-60.
36. Walker MC, Semyanov A. Regulation of excitability by extrasynaptic GABA(A) receptors. Results Probl Cell Differ 2008; 44: 29-48.
37. Semyanov A, Walker MC, Kullmann DM, Silver RA. Tonically active GABA A receptors: modulating gain and maintaining the tone. Trends Neurosci 2004; 27(5): 262-9.
38. Rudolph U, Knoflach F. Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat Rev Drug Discov 2011; 10(9): 685-97.
39. Zeilhofer HU, Benke D, Yevenes GE. Chronic pain States: pharmacological strategies to restore diminished inhibitory spinal pain control. Annu Rev Pharmacol Toxicol 2012; 52: 111-33.
40. Zarnowska ED, Keist R, Rudolph U, Pearce RA. GABAA receptor alpha5 subunits contribute to GABAA, slow synaptic inhibition in mouse hippocampus. J Neurophysiol 2009; 101(3): 1179-91.
41. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I. Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc Natl Acad Sci USA 2003; 100(24): 14439-44.
42. Curtis DR, Phillis JW, Watkins JC. The depression of spinal neurones by gamma-amino-n-butyric acid and beta-alanine. J Physiol 1959; 146(1): 185-203.
43. Eccles JC, Schmidt R, Willis WD. Pharmacological studies on presynaptic inhibition. J Physiol 1963; 168: 500-30.
44. Schmidt RF. Presynaptic inhibition in the vertebrate central nervous system. Ergeb Physiol 1971; 63: 20-101.
45. Kaufman DL, McGinnis JF, Krieger NR, Tobin AJ. Brain glutamate decarboxylase cloned in lambda gt-11: fusion protein produces gamma-aminobutyric acid. Science 1986; 232: 1138-40.
46. Erlander MG, Tillakaratne NJK, Feldblum S, Patel N, Tobin AJ. Two genes encode distinct glutamate decarboxylases. Neuron 1991; 7: 91-100.
47. Erlander MG, Tobin AJ. The structural and functional heterogeneity of glutamic acid decarboxylase: a review. Neurochem Res 1991; 16: 215-26.
48. Kaufman DL, Houser CR, Tobin AJ. Two forms of the gammaaminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem 1991; 56: 720-3.
49. McLaughlin BJ, Barber R, Saito K, Roberts E, Wu JY. Immunocytochemical localization of glutamate decarboxylase in rat spinal cord. J Comp Neurol 1975; 164: 305-21.
50. Barber RP, Vaughn JE, Roberts E. The cytoarchitecture of GABAergic neurons in rat spinal cord. Brain Res 1982; 238(2): 305-28.
51. Feldblum S, Erlander MG, Tobin AJ. Different distributions of GAD65 and GAD67 mRNAs suggest that the two glutamate decarboxylases play distinctive functional roles. J Neurosci Res 1993; 34: 689-706.
52. Feldblum S, Dumoulin A, Anoal M, Sandillon F, Privat A. Comparative distribution of GAD65 and GAD67 mRNAs and proteins in the rat spinal cord supports a differential regulation of these two glutamate decarboxylases in vivo. J Neurosci Res 1995; 42: 742-57.
53. Ma W, Behar T, Chang L, Barker JL. Transient increase in expression of GAD65 and GAD67 mRNAs during postnatal development of rat spinal cord. J Comp Neurol 1994; 346(1): 151-60.
54. Dougherty KJ, Sawchuk MA, Hochman S. Phenotypic Diversity and Expression of GABAergic Inhibitory Interneurons During Postnatal Development in Lumbar Spinal Cord of GAD67-GFP Mice. Neuroscience 2009; 163(3): 909-19.
55. Gao BX, Stricker C, Ziskind-Conhaim L. Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks. J Neurophysiol 2001; 86(1): 492-502.
56. Carlton SM, Hayes ES. Light microscopic and ultrastructural analysis of GABA-immunoreactive profiles in the monkey spinal cord. J Comp Neurol 1990; 300(2): 162-82.
57. Magoul R, Onteniente B, Geffard M, Calas A. Anatomical distribution and ultrastructural organization of the GABAergic system in the rat spinal cord. An immunocytochemical study using anti-GABA antibodies. Neuroscience 1987; 20(3): 1001-9.
58. Hughes DI, Mackie M, Nagy GG, et al. P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxylase-65 and originate from cells in deep medial dorsal horn. Proc Natl Acad Sci USA 2005; 102(25): 9038-43.
59. Sapin E, Lapray D, Bérod A, Goutagny R, Léger L, Ravassard P et al. Localization of the brainstem GABAergic neurons controlling paradoxical (REM) sleep. PLoS One [serial on the Internet]. 2009 Jan 26; 4(1): [about 10 screems]. Available from: http: //www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.po ne.0004272.
60. Berger AJ. Development of synaptic transmission to respiratory motoneurons. Respir Physiol Neurobiol 2011; 179(1): 34-42.
61. Wisden W, Gundlach AL, Barnard EA, Seeburg PH, Hunt SP. Distribution of GABAA receptor subunit mRNAs in rat lumbar spinal cord. Brain Res Mol Brain Res 1991; 10(2): 179-83.
62. Ruano D, Létang V, Biton B, et al. Subunit composition of rat ventral spinal cord GABA(A) receptors, assessed by single cell RTmultiplex PCR. Neuroreport 2000; 11(14): 3169-73.
63. Mody I, Pearce RA. Diversity of inhibitory neurotransmission through GABA(A) receptors. Trends Neurosci 2004; 27(9): 569-75.
64. Persohn E, Malherbe P, Richards JG. In situ hybridization histochemistry reveals a diversity of GABAA receptor subunit mRNAs in neurons of the rat spinal cord and dorsal root ganglia. Neuroscience 1991; 42(2): 497-507.
65. Ma W, Saunders PA, Somogyi R, Poulter MO, Barker JL. Ontogeny of GABAA receptor subunit mRNAs in rat spinal cord and dorsal root ganglia. J Comp Neurol 1993; 338(3): 337-59.
66. Petri S, Schmalbach S, Grosskreutz J, et al. The cellular mRNA expression of GABA and glutamate receptors in spinal motor neurons of SOD1 mice. J Neurol Sci 2005; 238(1-2): 25-30.
67. Serafini R, Maric D, Maric I, et al. Dominant GABA(A) receptor/ Cl-channel kinetics correlate with the relative expressions of alpha2, alpha3, alpha5 and beta3 subunits in embryonic rat neurones. Eur J Neurosci 1998; 10(1): 334-49.
68. Whiting PJ, McAllister G, Vassilatis D, et al. Neuronally restricted RNA splicing regulates the expression of a novel GABAA receptor subunit conferring atypical functional properties. J Neurosci 1997; 7(13): 5027-37.
69. Pape JR, Bertrand SS, Lafon P, et al. Expression of GABA(A) receptor alpha3-, theta-, and epsilon-subunit mRNAs during rat CNS development and immunolocalization of the epsilon subunit in developing postnatal spinal cord. Neuroscience 2009; 160(1): 85-96.
70. Bowery NG, Hudson AL, Price GW. GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 1987; 20(2): 365-83.
71. Richards JG, Schoch P, Häring P, Takacs B, Möhler H. Resolving GABAA/benzodiazepine receptors: cellular and subcellular localization in the CNS with monoclonal antibodies. J Neurosci 1987; 7(6): 1866-86.
72. Waldvogel HJ, Faull RL, Jansen KL, et al. GABA, GABA receptors and benzodiazepine receptors in the human spinal cord: an autoradiographic and immunohistochemical study at the light and electron microscopic levels. Neuroscience 1990; 39(2): 361-85.
73. Fritschy JM, Benke D, Mertens S, Oertel WH, Bachi T, Möhler H. Five subtypes of type A gamma-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies. Proc Natl Acad Sci USA 1992; 89(15): 6726-30.
74. Brickley SG, Mody I. Extrasynaptic GABA(A) receptors: their function in the CNS and implications for disease. Neuron 2012; 73(1): 23-34.
75. Alvarez FJ, Taylor-Blake B, Fyffe RE, De Blas AL, Light AR. Distribution of immunoreactivity for the beta 2 and beta 3 subunits of the GABAA receptor in the mammalian spinal cord. J Comp Neurol 1996; 365(3): 392-412.
76. Sur C, Mckernan R, Triller A. Subcellular localization of the GABAA receptor gamma 2 subunit in the rat spinal cord. Eur J Neurosci 1995; 7: 1323-32.
77. Geiman EJ, Zheng W, Fritschy JM, Alvarez FJ. Glycine and GABA(A) receptor subunits on Renshaw cells: relationship with presynaptic neurotransmitters and postsynaptic gephyrin clusters. J Comp Neurol 2002; 444(3): 275-89.
78. Todd AJ, Watt C, Spike RC, Sieghart W. Colocalization of GABA, glycine, and their receptors at synapses in the rat spinal cord. J Neurosci 1996; 16(3): 974-82.
79. Bohlhalter S, Weinmann O, Mohler H, Fritschy JM. Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord: an immunohistochemical study. J Neurosci 1996; 16(1): 283-97.
80. Waldvogel HJ, Baer K, Eady E, et al. Differential localization of gamma-aminobutyric acid type A and glycine receptor subunits and gephyrin in the human pons, medulla oblongata and uppermost cervical segment of the spinal cord: an immunohistochemical study. J Comp Neurol 2010; 518(3): 305-28.
81. Gutiérrez A, Khan ZU, De Blas AL. Immunocytochemical localization of the alpha 6 subunit of the gamma-aminobutyric acidA receptor in the rat nervous system. J Comp Neurol 1996; 365(3): 504-10.
82. Fritschy JM, Mohler H. GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits. J Comp Neurol 1995; 359(1): 154-94.
83. Lorenzo LE, Russier M, Barbe A, Fritschy JM, Bras H. Differential organization of gamma-aminobutyric acid type A and glycine receptors in the somatic and dendritic compartments of rat abducens motoneurons. J Comp Neurol 2007; 504(2): 112-26.
84. Yang J, Zorumski CF. Trifluoperazine blocks GABA-gated chloride currents in cultured chick spinal cord neurons. J Neurophysiol 1989; 61(2): 363-73.
85. Chub N, ÓDonovan MJ. Post-episode depression of GABAergic tranmission in spinal neurons of the chick embryo. J Neurophysiol 2001; 85(5): 2166-76.
86. Takahashi A, Mashimo T, Uchida I. GABAergic tonic inhibition of substantia gelatinosa neurons in mouse spinal cord. Neuroreport 2006; 17(12): 1331-5.
87. Ataka T, Gu JG. Relationship between tonic inhibitory currents and phasic inhibitory activity in the spinal cord lamina II region of adult mice. Mol Pain 2006; 2: [about 6 screens] Available from: http: //www.molecularpain.com/content/2/1/36.
88. Mitchell EA, Gentet LJ, Dempster J, Belelli D. GABAA and glycine receptor-mediated transmission in rat lamina II neurones: rele vance to the analgesic actions of neuroactive steroids. J Physiol 2007; 583(3): 1021-40.
89. Maeda A, Katafuchi T, Oba Y, Shiokawa H, Yoshimura M. Enhancement of GABAergic tonic currents by midazolam and noradrenaline in rat substantia gelatinosa neurons in vitro. Anesthesiology 2010; 113(2): 429-37.
90. Grasshoff C, Netzhammer N, Schweizer J, Antkowiak B, Hentschke H. Depression of spinal network activity by thiopental: shift from phasic to tonic GABA(A) receptor-mediated inhibition. Neuropharmacology 2008; 55(5): 793-802.
91. Castro A, Aguilar J, González-Ramírez R, et al. Tonic inhibition in spinal ventral horn interneurons mediated by α5 subunit-containing GABAA receptors. Biochem Biophys Res Commun 2011; 412(1): 26-31.
92. Wang L, Spary E, Deuchars J, Deuchars SA. Tonic GABAergic inhibition of sympathetic preganglionic neurons: a novel substrate for sympathetic control. J Neurosci 2008; 28(47): 12445-52.
93. Semyanov A, Walker MC, Kullmann DM. GABA uptake regulates cortical excitability via cell type-specific tonic inhibition. Nat Neurosci 2003; 6(5): 484-90.
94. Walker MC. GABAA receptor subunit specificity: a tonic for the excited brain. J Physiol 2008; 586(4): 921-2.
95. Han SM, Youn DH. GABAA receptor-mediated tonic currents in substantia gelatinosa neurons of rat spinal trigeminal nucleus pars caudalis. Neurosci Lett 2008; 441(3): 296-301.
96. Nusser Z, Mody I. Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells. J Neurophysiol 2002; 87(5): 2624-8.
97. Bonin RP, Labrakakis C, Eng DG, Whissell PD, De Koninck Y, Orser BA. Pharmacological enhancement of O-subunit-containing GABA(A) receptors that generate a tonic inhibitory conductance in spinal neurons attenuates acute nociception in mice. Pain 2011; 152(6): 1317-26.
98. Gao H, Smith BN. Tonic GABAA receptor-mediated inhibition in the rat dorsal motor nucleus of the vagus. J Neurophysiol 2010; 103(2): 904-14.
99. Kohno T, Wakai A, Ataka T, Ikoma M, Yamakura T, Baba H. Actions of midazolam on excitatory transmission in dorsal horn neurons of adult rat spinal cord. Anesthesiology 2006; 104(2): 338-43.
100. Kinkead R, Balon N, Genest SE, Gulemetova R, Laforest S, Drolet G. Neonatal maternal separation and enhancement of the inspiratory (phrenic) response to hypoxia in adult rats: disruption of GABAergic neurotransmission in the nucleus tractus solitarius. Eur J Neurosci 2008; 27(5): 1174-88.
101. Ruggeri P, Cogo CE, Picchio VV, Molinari C, Ermirio R, Calaresu FR. Influence of GABAergic mechanisms on baroreceptor inputs to nucleus tractus solitarii of rats. Am J Physiol 1996; 271: H931-6.
102. Hoop B, Beagle JL, Maher TJ, Kazemi H. Brain stem amino acid neurotransmitters and hypoxic ventilatory response. Respir Physiol 1999; 118: 117-29.
103. Gliddon CM, Darlington CL, Smith PF. GABAergic systems in the vestibular nucleus and their contribution to vestibular compensation. Prog Neurobiol 2005; 75: 53-81.
104. De Novellis V, Marabese I, Palazzo E, et al. Group I metabotropic glutamate receptors modulate glutamate and gamma-aminobutyric acid release in the periaqueductal gray neurons. Biochem Biophys Res Commun 2003; 302: 233-7.
105. Zhang J, Suneja SK, Potashner SJ. Protein kinase A and calcium/ calmodulin-dependent protein kinase II regulate glycine and GABA release in auditory brain stem nuclei. J Neurosci Res 2004; 75: 361-70.
106. McDougall SJ, Bailey TW, Mendelowitz D, Andresen MC. Propofol enhances both tonic and phasic inhibitory currents in secondorder neurons of the solitary tract nucleus (NTS). Neuropharmacology 2008; 54(3): 552-63.
107. Saper CB. The central autonomic nervous system: Conscious visceral perception and autonomic pattern generation. Annu Rev Neurosci 2002; 25: 433-69.
108. Andresen MC, Doyle MW, Bailey TW, Jin YH. Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius. Braz J Med Biol Res 2004; 37(4): 549-58.
109. Guyenet PG. The sympathetic control of blood pressure. Nat Rev Neurosci 2006; 7(5): 335-346.
110. Travagli RA, Hermann GE, Browning KN, Rogers RC. Brainstem circuits regulating gastric function. Annu Rev Physiol 2006; 68: 279-305.
111. Wang X. Propofol and isoflurane enhancement of tonic gammaaminobutyric acid type a current in cardiac vagal neurons in the nucleus ambiguus. Anesth Analg 2009; 108(1): 142-8.
112. Bouairi E, Kamendi H, Wang X, Gorini C, Mendelowitz D. Multiple types of GABAA receptors mediate inhibition in brain stem parasympathetic cardiac neurons in the nucleus ambiguus. J Neurophysiol 2006; 96(6): 3266-72.
113. Lopez de Armentia M, Cabanes C, Belmonte C. Electrophysiological properties of identified trigeminal ganglion neurons innervating the cornea of the mouse. Neuroscience 2000; 101: 1109-15.
114. Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC. Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J Neurosci 2005; 25(43): 10016-24.
115. Sivarao DV, Krowicki ZK, Hornby PJ. Role of GABAA receptors in rat hindbrain nuclei controlling gastric motor function. Neurogastroenterol Motil 1998; 10(4): 305-13.
116. Washabau RJ, Fudge M, Price WJ, Barone FC. GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function. Brain Res Bull 1995; 38(6): 587-94.
117. Gao H, Smith B. Zolpidem modulation of phasic and tonic GABA currents in the rat dorsal motor nucleus of the vagus. Neuropharmacology 2010; 58: 1220-7.
118. Tang ZQ, Dinh EH, Shi W, Lu Y. Ambient GABA-Activated Tonic Inhibition Sharpens Auditory Coincidence Detection via a Depolarizing Shunting Mechanism. J Neurosci 2011; 31(16): 6121-31.
119. Numata JM, Van Brederode JF, Berger AJ. Lack of an Endogenous GABAA-Receptor-Mediated Tonic Current in Hypoglossal Motoneurons. J Physiol 2012; 590(13): 2965-76.
120. Ornung G, Ottersen OP, Cullheim S, Ulfhake B. Distribution of glutamate-, glycine-and GABA-immunoreactive nerve terminals on dendrites in the cat spinal motor nucleus. Exp Brain Res 1998; 118: 517-32.
121. Rekling JC, Funk GD, Bayliss DA, Dong XW, Feldman JL. Synaptic control of motoneuronal excitability. Physiol Rev 2000; 80(2): 767-852.
122. Peng YY, Frank E. Activation of GABAA receptors causes presynaptic and postsynaptic inhibition at synapses between muscle spindle afferents and motoneurons in the spinal cord of bullfrogs. J Neurosci 1989; 9(5): 1516-22.
123. Delgado-Lezama R, Aguilar J, Cueva-Rolón R. Synaptic strength between motoneurons and terminals of the dorsolateral funiculus is regulated by GABA receptors in the turtle spinal cord. J Neurophysiol 2004; 91(1): 40-47.
124. Rudomin P, Jiménez I, Enriquez M. Effects of stimulation of group I afferents from flexor muscles on heterosynaptic facilitation of monosynaptic reflexes produced by Ia and descending inputs: a test for presynaptic inhibition. Exp Brain Res 1991; 85(1): 93-102.
125. Curtis DR, Malik R. The effect of GABA on lumbar terminations of rubrospinal neurons in the cat spinal cord. Proc R Soc Lond B Biol Sci 1984; 223(1230): 25-33.
126. Curtis DR, Wilson VJ, Malik R. The effect of GABA on the terminations of vestibulospinal neurons in the cat spinal cord. Brain Res 1984; 295(2): 372-5.
127. Glykys J, Mann EO, Mody I. Which GABA(A) receptor subunits are necessary for tonic inhibition in the hippocampus? J Neurosci 2008; 28(6): 1421-6.
128. Castro A, Aguilar J, Andrés C, Felix R, Delgado-Lezama R. GABAA receptors mediate motoneuron tonic inhibition in the turtle spinal cord. Neuroscience 2011; 192: 74-80.
129. Tegner J, Matsushima T, El Manira A, Grillner S. Th espinal GABA system modulates burst frequency and intersegmental coordination in the lamprey: differential effects of GABAA and GABAB receptors. J Neurophysiol 1993; 69: 647-57.
130. Cazalets JR, Sqalli-Houssaini Y, Clarac F. GABAergic inactivation of the central pattern generators for locomotion in isolated neonatal rat spinal cord. J Physiol 1994; 474: 173-81.
131. Cowley KC, Schmidt BJ. Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neontal rat spinal cord. J Neurophysiol 1995; 74: 1109-17.
132. Kremer E, Lev-Tov A. Localization of the spinal network associated with generation of hindlimb locomotion in the neonatal rat and organization of its transverse coupling system. J Neurophysiol 1997; 77: 1155-70.
133. Bertrand S, Cazalets JR. GABAA and GABAB modulation of synaptic transmission between L1-L2 locomotor network and the motoneurons in the newborn rat isolated spinal cord. Ann NY Acad Sci 1998; 16: 470-1.
134. Schmitt DE, Hill RH, Grillner S. The spinal GABAergic system is a strong modulator of burst frequency in the lamprey locomotor network. J Neurophysiol 2004; 92: 2357-67.
135. Frank K, Fourtes MGF. Presynaptic and postsynaptic inhibition of monosynaptic reflexes. Fed Proc 1957; 16: 39-40.
136. Eccles JC. Presynaptic Inhibition in the spinal cord. Prog Brain Res 1964; 12: 65-91.
137. Alvarez FJ. Anatomical basis for presynaptic inhibition of primary sensory fibers. In: Rudomin P, Romo R, Mendell LM. Eds. Presynaptic inhibition and neural control. Oxford University Press, New York 1998; pp. 13-49.
138. Bautista W, Aguilar J, Loeza-Alcocer JE, Delgado-Lezama R. Preand postsynaptic modulation of monosynaptic reflex by GABAA receptors on turtle spinal cord. J Physiol 2010; 588: 2621-31.
139. Hamann M, Rossi DJ, Attwell D. Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 2002; 33: 625-33.
140. De Groat WC, Lalley PM, Saum WR. Depolarization of dorsal root ganglia in the cat by GABA and related amino acids: antagonism by picrotoxin and bicuculline. Brain Res 1972; 44(1): 273-7.
141. Feltz P, Rasminsky M. A model for the mode of action of GABA on primary afferent terminals: Depolarizing effects of GABA applied iontophoretically to neurons of mammalian dorsal root ganglia. Neuropharmacology 1974; 13: 553-63.
142. Levy RA. GABA: a direct depolarizing action at the mammalian primary afferent terminal. Brain Res 1974; 76(1): 155-60.
143. Brown DA, Marsh S. Axonal GABA-receptors in mammalian peripheral nerve trunks. Brain Res 1978; 158: 187-91.
144. Morris M, Di Costanzo G, Fox S, Werman R. Depolarizing action of GABA gamma-aminobutyric acid on myelinated fibers of peripheral nerve. Brain Res 1983; 278: 117-26.
145. Labrakakis C, Tong CK, Weissman T, Torsney C, MacDermott AB. Localization and function of ATP and GABAA receptors expressed by nociceptors and other postnatal sensory neurons in rat. J Physiol 2003; 549(1): 131-42.
146. Sakatani K, Chesler M, Hassan AZ. GABAA receptors modulate axonal conduction in dorsal columns of neonatal rat spinal cord. Brain Res 1991; 542(2): 273-9.
147. Saruhashi Y, Young W, Sugimori M, Abrahams J, Sakuma J. GABA increases refractoriness of adult rat dorsal column axons. Neuroscience 1999; 94(4): 1207-12.
148. Witschi R, Punnakkal P, Paul J, et al. Presynaptic alpha2-GABAA receptors in primary afferent depolarization and spinal pain control. J Neurosci 2011; 31(22): 8134-42.
149. Singer E, Placheta P. Reduction of [3H]muscimol binding sites in rat dorsal spinal cord after neonatal capsaicin treatment. Brain Res 1980; 202(2): 484-7.
150. Carlton SM, Zhou S, Coggeshall RE. Peripheral GABA(A) receptors: evidence for peripheral primary afferent depolarization. Neuroscience 1999; 93(2): 713-22.
151. Furuyama T, Sato M, Sato K, Araki T, Inagaki S, Takagi H et al. Co-expression of glycine receptor beta subunit and GABAA receptor gamma subunit mRNA in the rat dorsal root ganglion cells. Brain Res Mol Brain Res 1992; 12(4): 335-8.
152. Paul J, Zeilhofer HU, Fritschy JM. Selective distribution of GABA(A) receptor subtypes in mouse spinal dorsal horn neurons and primary afferents. J Comp Neurol 2012; 520(17): 3895-911.
153. Loeza-Alcocer J, Aguilar J, González-Ramírez R, Felix R, Delgado-Lezama R. Modulation of the dorsal root and the monosynaptic reflex by high affinity α5 subunit-containing GABAA receptors in the turtle spinal cord. In the Annual Meeting of the Society for Neuroscience, San Diego, CA in November 15th 2010.
154. Errington AC, Cope DW, Crunelli V. Augmentation of Tonic GABA(A) Inhibition in Absence Epilepsy: Therapeutic Value of Inverse Agonists at Extrasynaptic GABA(A) Receptors. Adv Pharmacol Sci [serial on the internet]. 2011 Sep 5; 2011: [about 12 screens]. Available from: http: //www.hindawi.com/journals/aps/2011/790590.
155. Knabl J, Witschi R, Hösl K, et al. Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature 2008; 451(7176): 330-4.