Epilepsy, E/I balance and GABAA receptor plasticity

Frontiers in Molecular Neuroscience

Volumn 1, Issue MAR, 2008, Pages

  Fritschy, Jean Marc ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Absence epilepsy; Homeostatic plasticity; Synaptic plasticity; Temporal lobe epilepsy; Tonic inhibition

Indexed keywords

EID: 84890883246     PISSN: 16625099     EISSN: None     Source Type: Journal    
DOI: 10.3389/neuro.02.005.2008     Document Type: Article

References (122)

1. Audenaert, D., Schwartz, E., Claeys, K. G., Claes, L., Deprez, L., Suls, A., Van Dyck, T., Lagae, L., Van Broeckhoven, C., Macdonald, R. L., and De Jonghe, P. (2006). A novel GABRG2 mutation associated with febrile seizures. Neurology 67, 687-690.
2. Baulac, S., Huberfeld, G., Gourfinkel-An, I., Mitropoulou, G., Beranger, A., Prud'homme, J. F., Baulac, M., Brice, A., Bruzzone, R., and LeGuern, E. (2001). First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the i2-subunit gene. Nat. Genet. 28, 46-48.
3. Belelli, D., and Herd, M. B. (2003). The contraceptive agent Provera enhances GABAA receptor-mediated inhibitory neurotransmission in the rat hippocampus: evidence for endogenous neurosteroids? J. Neurosci. 23, 10013-10020.
4. Belelli, D., Peden, D. R., Rosahl, T. W., Wafford, K. A., and Lambert, J. J. (2005). Extrasynaptic GABAA receptors of thalamocortical neurons: a molecular target for hypnotics. J. Neurosci. 25, 11513-11520.
5. Ben-Ari, Y., Trembaly, E., and Ottersen, O. P. (1980). Injections of kainic acid into the amygdaloid complex of the rat: an electrographic, clinical and histological study in relation to the pathology of epilepsy. Neuroscience 5, 515-528.
6. Bessaih, T., Bourgeais, L., Badiu, C. I., Carter, D. A., Toth, T. I., Ruano, D., Lambolez, B., Crunelli, V., and Leresche, N. (2006). Nucleus-specific abnormalities of GABAergic synaptic transmission in a genetic model of absence seizures. J. Neurophysiol. 96, 3074-3081.
7. Blatow, M., Caputi, A., and Monyer, H. (2005). Molecular diversity of neocortical GABAergic interneurones. J. Physiol. (Lond.) 562, 99-105.
8. Bonin, R. P., Martin, L. J., Macdonald, J. F., and Orser, B. A. (2007). B5-GABAA receptors regulate the intrinsic excitability of mouse hippocampal pyramidal neurons. J. Neurophysiol. 98, 2244-2254.
9. Bowser, D. N., Wagner, D. A., Czajkowski, C., Cromer, B. A., Parker, M. W., Wallace, R. H., Harkin, L. A., Mulley, J. C., Marini, C., Berkovic, S. F., Williams, D. A., Jones, M. V., and Petrou, S. (2002). Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation (r2(R43Q) found in human epilepsy. Proc. Natl. Acad. Sci. U.S.A. 99, 15170-15175.
10. Bradford, H. F. (1995). Glutamate, GABA and epilepsy. Prog. Neurobiol. 47, 477-511.
11. Brünig, I., Penschuck, S., Berninger, B., Benson, J. A., and Fritschy, J. M. (2001). BDNF reduces miniature inhibitory postsynaptic currents by rapid down-regulation of GABAA receptor surface expression. Eur. J. Neurosci. 13, 1320-1328.
12. Brussaard, A. B., and Herbison, A. E. (2000). Long-term plasticity of postsynaptic GABAA-receptor function in the adult brain: insights from the oxytocin neurone. Trends Neurosci. 23, 190-195.
13. Caraiscos, V. B., Elliott, E. M., You-Ten, K. E., Cheng, V. Y., Belelli, D., Newell, J. G., Jackson, M. F., Lambert, J. J., Rosahl, T. W., Wafford, K. A., MacDonald, J. F., and Orser, B. A. (2004). Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by i5 subunit-containing 5-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. U.S.A. 101, 3662-3667.
14. Cossart, R., Bernard, C., and Ben-Ari, Y. (2005). Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies. Trends Neurosci. 28, 108-115.
15. Cossette, P., Liu, L., Brisebois, K., Dong, H., Lortie, A., Vanasse, M., Saint-Hilaire, J. M., Carmant, L., Verner, A., Lu, W. Y., Wang, Y. T., and Rouleau, G. A. (2002). Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat. Genet. 31, 184-189.
16. Costantin, L., Bozzi, Y., Richichi, C., Viegi, A., Antonucci, F., Funicello, M., Gobbi, M., Mennini, T., Rossetto, O., Montecucco, C., Maffei, L., Vezzani, A., and Caleo, M. (2005). Antiepileptic effects of botulinum neurotoxin. Eur. J. Neurosci. 25, 1943-1951.
17. Coulter, D. A., McIntyre, D. C., and Loscher, W. (2002). Animal models of limbic epilepsies: what can they tell us? Brain Pathol. 12, 240-256.
18. Crestani, F., Keist, R., Fritschy, J. M., Benke, D., Vogt, K., Prut, L., Bluethmann, H., Mohler, H., and Rudolph, U. (2002). Trace fear conditioning involves hippocampal M5 GABAA receptors. Proc. Natl. Acad. Sci. U.S.A. 99, 8980-8985.
19. De Koninck, Y. (2007). Altered chloride homeostasis in neurological disorders: a new target. Curr. Opin. Pharmacol. 7, 93-99.
20. Dibbens, L. M., Feng, H. J., Richards, M. C., Harkin, L. A., Hodgson, B. L., Scott, D., Jenkins, M., Petrou, S., Sutherland, G. R., Scheffer, I. E., Berkovic, S. F., Macdonald, R. L., and Mulley, J. C. (2004). GABRD encoding a protein for extra-or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum. Mol. Genet. 13, 1315-1319.
21. Drasbek, K. R., and Jensen, K. (2005). THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex. Cereb. Cortex Epub:Oct 12 (ahead of print).
22. Essrich, C., Lorez, M., Benson, J. A., Fritschy, J. M., and Luscher, B. (1998). Postsynaptic clustering of major GABAA receptor subtypes requires the r2 subunit and gephyrin. Nat. Neurosci. 1, 563-571.
23. Eugène, E., Depienne, C., Baulac, S., Baulac, M., Fritschy, J. M., Le Guern, E., Miles, R., and Poncer, J. C. (2007). Synaptic and non-synaptic impact of GABRG2 mutations linked to human epileptic syndromes. J. Neurosci. 27, 14108-14116.
24. Farrant, M., and Kaila, K. (2007). The cellular, molecular and ionic basis of GABAA receptor signalling. Prog. Brain Res. 160, 59-87.
25. Farrant, M., and Nusser, Z. (2005). Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nat. Rev. Neurosci. 6, 215-229.
26. Fedi, M., Berkovic, S. F., Macdonell, R. A., Curatolo, J. M., Marini, C., and Reutens, D. C. (2007). Intracortical hyperexcitability in humans with a GABAA receptor mutation. Cereb. Cortex Epub:Jul 5 (ahead of print).
27. Feng, H. J., Kang, J. Q., Song, L., Dibbens, L., Mulley, J., and Macdonald, R. L. (2006). QQSubunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of a44222GABAA receptors. J. Neurosci. 26, 1499-1506.
28. Fiumelli, H., and Woodin, M. A. (2007). Role of activity-dependent regulation of neuronal chloride homeostasis in development. Curr. Opin. Neurobiol. 17, 81-86.
29. Frugier, G., Cousson, F., Giraud, M. J., Odessa, M. F., Emerit, M. B., Boué-Grabot, E., and Garret, M. (2007). A G2(R43Q) mutation, linked to epilepsy in humans, alters GABAA receptor assembly and modifies subunit composition on the cell surface. J. Biol. Chem. 282, 3819-3828.
30. Gale, K. (1992). GABA and epilepsy: basic concepts from preclinical research. Epilepsia 33, S3-S12.
31. Gall, C. M., and Lynch, G. (2004). Integrins, synaptic plasticity and epileptogenesis. Adv. Exp. Med. Biol. 548, 12-33.
32. Gallagher, M. J., Ding, L., Maheshwari, A., and Macdonald, R. L. (2007). The GABAA receptor r1 subunit epilepsy mutation A322D inhibits transmembrane helix formation and causes proteasomal degradation. Proc. Natl. Acad. Sci. U.S.A. 104, 12999-13004.
33. Gilbert, S. L., Zhang, L., Forster, M. L., Anderson, J. R., Iwase, T., Soliven, B., Donahue, L. R., Sweet, H. O., Bronson, R. T., Davisson, M. T., Wollmann, R. L., and Lahn, B. T. (2006). Trak1 mutation disrupts GABAA receptor homeostasis in hypertonic mice. Nat. Genet. 38, 245-250.
34. Gilby, K. L., Da Silva, E. A., and McIntyre, D. C. (2005). Differential GABAA subunit expression following status epilepticus in seizure-prone and seizure-resistant rats: a putative mechanism for refractory drug response. Epilepsia 46, 3-9.
35. Glykys, J., and Mody, I. (2006). Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABAA receptor r5 subunit-deficient mice. J. Neurophysiol. 95, 2796-2807.
36. Gulledge, A. T., and Stuart, G. J. (2003). Excitatory actions of GABA in the cortex. Neuron 37, 299-309.
37. Hanus, C., Ehrensperger, M. V., and Triller, A. (2006). Activity-dependent movements of postsynaptic scaffolds at inhibitory synapses. J. Neurosci. 26, 4586-4595.
38. Harkin, L. A., Bowser, D. N., Dibbens, L. M., Singh, R., Phillips, F., Wallace, R. H., Richards, M. C., Williams, D. A., Mulley, J. C., Berkovic, S. F., Scheffer, I. E., and Petrou, S. (2002). Truncation of the GABAA-receptor-2 subunit in a family with generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 70, 530-536.
39. Heron, S. E., Scheffer, I. E., Berkovic, S. F., Dibbens, L. M., and Mulley, J. C. (2007). Channelopathies in idiopathic epilepsy. Neurotherapeutics 4, 295-304.
40. Herring, D., Huang, R. Q., Singh, M., Robinson, L. C., Dillon, G. H., and Leidenheimer, N. J. (2003). Constitutive GABAA receptor endocytosis is dynamin-mediated and dependent on a dileucine AP2 adaptin-binding motif within the o2 subunit of the receptor. J. Biol. Chem. 278, 24046-24052.
41. Hinkle, D. J., and Macdonald, R. L. (2003). HHSubunit phosporylation selectivity increases fast desensitization and prolongs deactivation of f1 11 and 12L and a1 13 32L GABAA receptor currents. J. Neurosci. 23, 11698-11710.
42. Houser, C. R., and Esclapez, M. (2003). Downregulation of the H5 subunit of the GABAA receptor in the pilocarpine model of temporal lobe epilepsy. Hippocampus 13, 633-645.
43. Huberfeld, G., Wittner, L., Clemenceau, S., Baulac, M., Kaila, K., Miles, R., and Rivera, C. (2007). Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. J. Neurosci. 27, 9866-9873.
44. Huntsman, M. M., and Huguenard, J. R. (2006). Fast IPSCs in rat thalamic reticular nucleus require the GABAA receptor r1 subunit. J. Physiol. (Lond.) 572, 459-475.
45. Jones, A., Korpi, E. R., McKernan, R. M., Pelz, R., Nusser, Z., Makela, R., Mellor, J. R., Pollard, S., Bahn, S., Stephenson, F. A., Randall, A. D., Sieghart, W., Somogyi, P., Smith, A. J. H., and Wisden, W. (1997). Ligand-gated ion channel subunit partnerships: GABAA receptor r6 subunit gene inactivation inhibits 66subunit expression. J. Neurosci. 17, 1350-1362.
46. Jovanovic, J. N., Thomas, P., Kittler, J. T., Smart, T. G., and Moss, S. J. (2004). Brainderived neurotrophic factor modulates fast synaptic inhibition by regulating GABAA receptor phosphorylation, activity, and cell-surface stability. J. Neurosci. 24, 522-530.
47. Kananura, C., Haug, K., Sander, T., Runge, U., Gu, W., Hallmann, K., Rebstock, J., Heils, A., and Steinlein, O. K. (2002). A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions. Arch. Neurol. 59, 1137-1141.
48. Kanematsu, T., Yasunaga, A., Mizoguchi, Y., Kuratani, A., Kittler, J. T., Jovanovic, J. N., Takenaka, K., Nakayama, K. I., Fukami, K., Takenawa, T., Moss, S. J., Nabekura, J., and Hirata, M. (2006). Modulation of GABAA receptor phosphorylation and membrane trafficking by phospholipase C-related inactive protein/protein phosphatase 1 and 2A signaling complex underlying BDNF-dependent regulation of GABAergic inhibition. J. Biol. Chem. 281, 22180-22189.
49. Kang, J. Q., Shen, W., and Macdonald, L. (2006). Why does fever trigger febrile seizures? GABAA receptor r2 subunit mutations associated with idiopathic generalized epilepsies have temperature-dependent trafficking deficiencies. J. Neurosci. 26, 2590-2597.
50. Kapur, J., and Macdonald, R. L. (1996). Pharmacological properties of K-aminobutyric acidA receptors from acutely dissociated rat dentate granule cells. Mol. Pharmacol. 50, 458-466.
51. Keller, C. A., Yuan, X., Panzanelli, P., Martin, M. L., Alldred, M., Sassoe-Pognetto, M., and Luscher, B. (2004). The L2 subunit of GABAA receptors is a substrate for palmitoylation by GODZ. J. Neurosci. 24, 5881-5891.
52. Kittler, J. T., and Moss, S. J. (2001). Neurotransmitter receptor trafficking and the regulation of synaptic strength. Traffic 2, 437-448.
53. Kittler, J. T., and Moss, S. J. (2003). Modulation of GABAA receptor activity by phosphorylation and receptor trafficking: implications for the efficacy of synaptic inhibition. Curr. Opin. Neurol. 13, 341-347.
54. Kneussel, M., and Loebrich, S. (2007). Trafficking and synaptic anchoring of ionotropic inhibitory neurotransmitter receptors. Biol. Cell. 99, 297-309.
55. Krogsgaard-Larsen, P., Frolund, B., Liljefors, T., and Ebert, B. (2004). GABAA agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic. Biochem. Pharmacol. 68, 1573-1580.
56. Kuipers, S. D., and Bramham, C. R. (2006). Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr. Opin. Drug Discov. Devel. 9, 580-586.
57. Lagrange, A. H., Botzolakis, E. J., and Macdonald, R. L. (2007). Enhanced macroscopic desensitization shapes the response of d4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA. J. Physiol. (Lond.) 578, 655-676.
58. Lee, H. H., Walker, J. A., Williams, J. R., Goodier, R. R., Payne, J. A., and Moss, S. J. (2007). Direct PKC-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter, KCC2. J. Biol. Chem. 282, 29777-29784.
59. Lenzen, K. P., Heils, A., Lorenz, S., Hempelmann, A., and Sander, T. (2005). Association analysis of the Arg220His variation of the human gene encoding the GABA delta subunit with idiopathic generalized epilepsy. Epilepsy Res. 65, 53-57.
60. Li, H., Wu, J., Huguenard, J. R., and Fisher, R. S. (2006). Selective changes in thalamic and cortical GABAA receptor subunits in a model of acquired absence epilepsy in the rat. Neuropharmacology 51, 121-128.
61. Liu, X. B., Coble, J., van Luijtelaar, G., and Jones, E. G. (2007). Reticular nucleus-specific changes in c3 subunit protein at GABA synapses in genetically epilepsy-prone rats. Proc. Natl. Acad. Sci. U.S.A. 104, 12512-12517.
62. Loup, F., Picard, F., André, V. M., Kehrli, P., Yonekawa, Y., Wieser, H. G., and Fritschy, J. M. (2006). Altered expression of (3-containing GABAA receptors in the neocortex of patients with focal epilepsy. Brain 129, 3277-3289.
63. Loup, F., Wieser, H. G., Yonekawa, Y., Aguzzi, A., and Fritschy, J. M. (2000). Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy. J. Neurosci. 20, 5401-5419.
64. Luscher, B., and Fritschy, J. M. (2001). Subcellular localization and regulation of GABAA receptors and associated proteins. Int. Rev. Neurobiol. 48, 31-64.
65. Magloczky, Z., and Freund, T. F. (2005). Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci. 28, 334-340.
66. Maguire, J. L., Stell, B. M., Rafizadeh, M., and Mody, I. (2005). Ovarian cycle-linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat. Neurosci. 8, 797-804.
67. Makela, R., Uusi-Oukari, M., Homanics, G. E., Quinlan, J. J., Firestone, L. L., Wisden, W., and Korpi, E. R. (1997). Cerebellar a-aminobutyric acid type A receptors: pharmacological subtypes revealed by mutant mouse lines. Mol. Pharmacol. 52, 380-388.
68. Maljevic, S., Krampfl, K., Cobilanschi, J., Tilgen, N., Beyer, S., Weber, Y. G., Schlesinger, F., Ursu, D., Melzer, W., Cossette, P., Bufler, J., Lerche, H., and Heils, A. (2006). A mutation in the GABAA receptor alpha1 subunit is associated with absence epilepsy. Ann. Neurol. 59, 983-987.
69. Man, H. Y., Lin, J., Ju, W. H., Ahmadian, G., Liu, L., Becker, L. E., Sheng, M., and Wang, Y. T. (2000). Regulation of AMPA receptor-mediated synaptic transmission by clathrindependent receptor internalization. Neuron 25, 649-662.
70. Mann, E. O., and Paulsen, O. (2007). Role of GABAergic inhibition in hippocampal network oscillations. Trends Neurosci. 30, 343-349.
71. Marder, E., and Goaillard, J. M. (2006). Variability, compensation and homeostasis in neuron and network function. Nat. Rev. Neurosci. 7, 563-574.
72. Markram, H., Toledo-Rodriguez, M., Wang, Y., Gupta, A., Silberberg, G., and Wu, C. (2004). Interneurons of the neocortical inhibitory system. Nat. Rev. Neurosci. 5, 793-807.
73. Marty, S., Wehrle, R., Fritschy, J. M., and Sotelo, C. (2004). Quantitative effects produced by modifications of neuronal activity on the size of GABAA receptor clusters in hippocampal slice cultures. Eur. J. Neurosci. 20, 427-440.
74. Marty, S., Wehrlé, R., and Sotelo, C. (2000). Neuronal activity and brain-derived neurotrophic factor regulate the density of inhibitory synapses in organotypic slice cultures of postnatal hippocampus. J. Neurosci. 20, 8087-8095.
75. Mody, I. (2005). Aspects of the homeostatic plasticity of GABAA receptor-mediated inhibition. J. Physiol. (Lond.) 562, 37-46.
76. Mody, I., and Pearce, R. A. (2004). Diversity of inhibitory neurotransmission through GABAA receptors. Trends Neurosci. 27, 569-575.
77. Nishimura, T., Schwarzer, C., Gasser, E., Kato, N., Vezzani, A., and Sperk, G. (2005). Altered expression of GABAA and GABAB receptor subunit mRNAs in the hippocampus after kindling and electrically induced status epilepticus. Neuroscience 134, 691-704.
78. Noebels, J. L. (2003). The biology of epilepsy genes. Annu. Rev. Neurosci. 26, 599-625.
79. Nusser, Z., Sieghart, W., and Somogyi, P. (1998). Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J. Neurosci. 18, 1693-1703.
80. Olsen, R. W., and Avoli, M. (1997). GABA and epileptogenesis. Epilepsia 38, 399-407.
81. Payne, J. A., Rivera, C., Voipio, J., and Kaila, K. (2003). Cation-chloride co-transporters in neuronal communication, development and trauma. Trends Neurosci. 26, 199-206.
82. Peng, Z., Hauer, B., Mihalek, R. M., Homanics, G. E., Sieghart, W., Olsen, R. W., and Houser, C. R. (2002). GABAA receptor changes in rrsubunit-deficient mice: Altered expression of e4 and 42 subunits in the forebrain. J. Comp. Neurol. 446, 179-197.
83. Peng, Z. C., Huang, C. S., Stell, B. M., Mody, I., and Houser, C. R. (2004). Altered expression of the d subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy. J. Neurosci. 24, 8629-8639.
84. Prenosil, G. A., Schneider Gasser, E. M., Rudolph, U., Keist, R., Fritschy, J. M., and Vogt, K. E. (2006). Specific subtypes of GABAA receptors mediate phasic and tonic forms of inhibition in hippocampal pyramidal neurons. J. Neurophysiol. 96, 846-857.
85. Price, T. J., Cervero, F., and de Koninck, Y. (2005). Role of cation-chloride-cotransporters (+) in pain and hyperalgesia. Curr. Top. Med. Chem. 5, 547-555.
86. Rathenberg, J., Kittler, J. T., and Moss, S. J. (2004). Palmitoylation regulates the clustering and cell surface stability of GABAA receptors. Mol. Cell. Neurosci. 26, 251-257.
87. Ratte, S., and Lacaille, J. C. (2006). Selective degeneration and synaptic reorganization of hippocampal interneurons in a chronic model of temporal lobe epilepsy. Adv. Neurol. 97, 69-76.
88. Rich, M. M., and Wenner, P. (2007). Sensing and expressing homeostatic synaptic plasticity. Trends Neurosci. 30, 119-125.
89. Rivera, C., Voipio, J., and Kaila, K. (2005). Two developmental switches in GABAergic signalling: the Ks-Cl--cotransporter KCC2 and carbonic anhydrase CAVII. J. Physiol. (Lond.) 562, 27-36.
90. Rivera, C., Voipio, J., Thomas-Crusells, J., Li, H., Emri, Z., Sipilä, S., Payne, J. A., Minichiello, L., Saarma, M., and Kaila, K. (2004). Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J. Neurosci. 24, 4683-4691.
91. Roberts, D. S., Raol, Y. H., Bandyopadhyay, S., Lund, I. V., Budreck, E. C., Passini, M. A., Wolfer, J. H., Brooks-Kayal, A. R., and Russek, S. J. (2005). Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced upregulation of GABAA receptor r4 subunit expression. Proc. Natl. Acad. Sci. U.S.A. 102, 11894-11899.
92. Rutherford, L. C., DeWan, A., Lauer, H. M., and Turrigiano, G. G. (1997). Brain-derived neurotrophic factor mediates the activity-dependent regulation of inhibition in neocortical cultures. J. Neurosci. 17, 4527-4535.
93. Sassoè-Pognetto, M., and Fritschy, J. M. (2000). Gephyrin, a major postsynaptic protein of GABAergic synapses. Eur. J. Neurosci. 7, 2205-2210.
94. Schweizer, C., Balsiger, S., Bluethmann, H., Mansuy, I. M., Fritschy, J. M., Mohler, H., and Luscher, B. (2003). The L2 subunit of GABAA receptors is required for maintenance of receptors at mature synapses. Mol. Cell. Neurosci. 24, 442-450.
95. Scimemi, A., Semyanov, A., Sperk, G., Kullmann, D. M., and Walker, M. C. (2005). Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J. Neurosci. 25, 10016-10024.
96. Semyanov, A., Walker, M. C., Kullmann, D. M., and Silver, R. A. (2004). Tonically active GABAA receptors: modulating gain and maintaining the tone. Trends Neurosci. 27, 262-269.
97. Shen, H., Gong, Q. H., Aoki, C., Yuan, M., Ruderman, Y., Dattilo, M., Williams, K., and Smith, S. S. (2007). Reversal of neurosteroid effects at S44222GABAA receptors triggers anxiety at puberty. Nat. Neurosci. 10, 469-477.
98. Sinkkonen, S. T., Vekovischeva, O. Y., Möykkynen, T., Ogris, W., Sieghart, W., Wisden, W., and Korpi, E. R. (2004). Behavioural correlates of an altered balance between synaptic und extrasynaptic GABAAergic inhibition in a mouse model. Eur. J. Neurosci. 20, 2168-2178.
99. Snead, O. C. (1992). Pharmacological models of generalized absence seizures in rodents. J. Neural Transm. Suppl. 35, 7-19.
100. Sperk, G. (1994). Kainic acid seizures in the rat. Prog. Neurobiol. 42, 1-32.
101. Spigelman, I., Li, Z., Banerjee, P. K., Mihalek, R. M., Homanics, G. E., and Olsen, R. W. (2002). Behavior and physiology of mice lacking the GABAA receptor rrsubunit. Epilepsia 43, 3-8.
102. Steiger, J. L., and Russek, S. J. (2004). GABAA receptors: building the bridge between subunit mRNAs, their promoters, and cognate transcription factors. Pharmacol. Ther. 101, 259-281.
103. Stell, B. M., Brickley, S. G., Tang, C. Y., Farrant, M., and Mody, I. (2003). Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by bbsubunit-containing GABAA receptors. Proc. Natl. Acad. Sci. U.S.A. 100, 14439-14444.
104. Storustovu, S. I., and Ebert, B. (2006). Pharmacological characterization of agonists at v-containing GABAA receptors: functional selectivity for extrasynaptic receptors is dependent on the absence of d2. J. Pharmacol. Exp. Ther. 316, 1351-1359.
105. Sun, C., Sieghart, W., and Kapur, J. (2004). Distribution of e1, 14, 42, and 22subunits of GABAA receptors in hippocampal granule cells. Brain Res. 1029, 207-216.
106. Szabadics, J., Varga, C., Molnar, G., Olah, S., Barzo, S., and Tamas, G. (2006). Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits. Science 311, 233-235.
107. Thomas, P., Mortensen, M., Hosie, A. M., and Smart, T. G. (2005). Dynamic mobility of functional GABAA receptors at inhibitory synapses. Nat. Neurosci. 8, 889-897.
108. 2+ oscillations with KCC2 mRNA downregulation in injured facial motoneurons. J. Neurophysiol. 89, 1353-1362.
109. Trasande, C. A., and Ramirez, J. M. (2007). Activity deprivation leads to seizures in hippocampal slice cultures: is epilepsy the consequence of homeostatic plasticity? J. Clin. Neurophysiol. 24, 154-164.
110. Triller, A., Cluzeaud, F., Pfeiffer, F., Betz, H., and Korn, H. (1985). Distribution of glycine receptors at central synapses: an immunoelectron microscopy study. J. Cell. Biol. 101, 683-688.
111. Tukker, J. J., Fuentealba, P., Hartwich, K., Somogyi, P., and Klausberger, T. (2007). Cell type-specific tuning of hippocampal interneuron firing during gamma oscillations in vivo. J. Neurosci. 27, 8184-8189.
112. Turrigiano, G. (2007). Homeostatic signaling: the positive side of negative feedback. Curr. Opin. Neurobiol. 17, 318-324.
113. van Luijtelaar, G., and Sitnikova, E. (2006). Global and focal aspects of absence epilepsy: the contribution of genetic models. Neurosci. Biobehav. Rev. 30, 983-1003.
114. van Rijnsoever, C., Sidler, C., and Fritschy, J. M. (2005). Internalized GABAA-receptor subunits are transferred to an intracellular pool associated with the postsynaptic density. Eur. J. Neurosci. 21, 327-338.
115. Wake, H., Watanabe, M., Moorhouse, A. J., Kanematsu, T., Horibe, S., Matsukawa, N., Asai, K., Ojika, K., Hirata, M., and Nabekura, J. (2007). Early changes in KCC2 phosphorylation in response to neuronal stress result in functional downregulation. J. Neurosci. 27, 1642-1650.
116. Wallace, R., Marini, C., Petrou, S., Harkin, L. A., Bowser, D. N., Panchal, R. G., Williams, D. A., Sutherland, G. R., Mulley, J. C., Scheffer, I. E., and Berkovic, S. F. (2001). Mutant GABAA receptor r2-subunit in childhood absence epilepsy and febrile seizures. Nat. Genet. 28, 49-52.
117. Wan, Q., Xiong, Z. G., Man, H. Y., Ackerley, C. A., Braunton, J., Lu, W. Y., Becker, L. E., MacDonald, J. F., and Wang, Y. T. (1997). Recruitment of functional GABAA receptors to postsynaptic domains by insulin. Nature 388, 686-690.
118. Wei, Z. W., Zhang, N., Peng, Z. C., Houser, C. R., and Mody, I. (2003). Perisynaptic localization of oosubunit-containing GABAA receptors and their activation by GABA spillover in the mouse dentate gyrus. J. Neurosci. 23, 10650-10661.
119. Wisden, W., Cope, D., Klausberger, T., Hauer, B., Sinkkonen, S. T., Tretter, V., Lujan, R., Jones, A., Korpi, E. R., Mody, I., Sieghart, W., and Somogyi, P. (2002). Ectopic expression of the GABAA receptor r6 subunit in hippocampal pyramidal neurons produces extrasynaptic receptors and an increased tonic inhibition. Neuropharmacology 43, 530-549.
120. Yu, W., Jiang, M., Miralles, C. P., Li, R., Chen, G., and de Blas, A. (2007). Gephyrin clustering is required for the stability of GABAergic synapses. Mol. Cell. Neurosci. 36, 484-500.
121. Zha, X. M., Green, S. H., and Dailey, M. E. (2005). Regulation of hippocampal synapse remodeling by epileptiform activity. Mol. Cell. Neurosci. 29, 494-506.
122. Zhang, N., Wei, W., Mody, I., and Houser, C. R. (2007). Altered localization of GABAA receptor subunits on dentate granule cell dendrites influences tonic and phasic inhibition in a mouse model of epilepsy. J. Neurosci. 27, 7520-7531.