REVIEW

Drosophila seizure disorders: genetic suppression of seizure susceptibility

  • Arunesh Saras 1 ,
  • Laura E. Simon 1 ,
  • Harlan J. Brawer 1 ,
  • Richard E. Price 2 ,
  • Mark A. Tanouye , 1,2,3
Expand
  • 1. Division of Organismal Biology, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720, USA
  • 2. Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
  • 3. Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA

Received date: 15 Feb 2016

Accepted date: 24 Mar 2016

Published date: 17 May 2016

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Various Drosophila models of human disease have recently received increased interest. The main goal is to uncover the fundamental biological basis for human pathology taking advantage of the power of Drosophila genetics. This review examines a set of Drosophila seizure-sensitive mutations that model human seizure disorders, especially epilepsy. Also described is a novel set of mutations that act as seizure-suppressors that ameliorate epilepsy phenotypes in double mutant combinations.

Cite this article

Arunesh Saras , Laura E. Simon , Harlan J. Brawer , Richard E. Price , Mark A. Tanouye . Drosophila seizure disorders: genetic suppression of seizure susceptibility[J]. Frontiers in Biology, 2016 , 11(2) : 96 -108 . DOI: 10.1007/s11515-016-1395-1

Acknowledgements

This study was supported by awards from the McKnight Foundation and the NIH (NS31231) to M.A.T. We thank the members of the Tanouye laboratory for helpful discussions throughout the project.
Arunesh Saras, Laura E. Simon, Harlan J. Brawer, Richard E. Price, Mark A. Tanouye declare that they have no conflict of interest.
This article does not contain any studies with human or vertebrate animal subjects performed by any of the authors.
1a
Barreto E, Cressman J R (2011). Ion concentration dynamics as a mechanism for neuronal bursting. J Biol Phys, 37(3): 361–373

1
Bassuk A G, Wallace R H, Buhr A, Buller A R, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach H L, Wu S, Nashelsky M, Vladar E K, Antic D, Ferguson P J, Cirak S, Voit T, Scott M P, Axelrod J D, Gurnett C, Daoud A S, Kivity S, Neufeld M Y, Mazarib A, Straussberg R, Walid S, Korczyn A D, Slusarski D C, Berkovic S F, El-Shanti H I (2008). A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet, 83(5): 572–581

DOI

2
Ben-Ari Y (2002). Excitatory actions of GABA during development: the nature of the nurture. Nature, 3: 728–739

3
Ben-Ari Y, Gaiarsa J L, Tyzio R, Khazipov R (2007). GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev, 87(4): 1215–1284

DOI

4
Benzer S (1971). From the gene to behavior. JAMA, 218(7): 1015–1022

DOI

5
Boettger T, Rust M B, Maier H, Seidenbecher T, Schweizer M, Keating D J, Faulhaber J, Ehmke H, Pfeffer C, Scheel O, (2003). Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J, 22(20): 5422–5434

DOI

6
Bullock T H, Horridge G A (1965). “Structure and Function in the Nervous System of Invertebrates”, 2 vol. San Francisco and London: W H Freeman A Comp Ltd, XXVIII, 1722pp

7
Carlson S D, Juang J L, Hilgers S L, Garment M B (2000). Blood barriers of the insect. Annu Rev Entomol, 45(1): 151–174

DOI

8
Catterall W A (2014). Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu Rev Pharmacol Toxicol, 54(1): 317–338

DOI

9
Catterall W A, Goldin A L, Waxman S G (2003). International Union of Pharmacology, XXXIX Compendium of voltage-gated ion channels: sodium channels. Pharmacol Rev, 55(4): 575–578

DOI

10
Champoux J J (2001). DNA topoisomerases: Structure, function and mechanism. Annu Rev Biochem, 70(1): 369–413

DOI

11
Chung H, Sztal T, Pasricha S, Sridhar M, Batterham P, Daborn P J (2009). Characterization of Drosophila melanogaster cytochrome P450 genes. Proc Natl Acad Sci USA, 106(14): 5731–5736

DOI

12
Chvatal A, Sykova E (2000). Glial influence on neuronal signaling. Prog Brain Res, 125: 199–216

DOI

13
Cressman J RJr, Ullah G, Ziburkus J, Schiff S J, Barreto E (2009). The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. single neuron dynamics. J Comput Neurosci, 26(2): 159–170

DOI

14
D'Ambrosio R (2004). The role of glial membrane ion channels in seizures and epileptogenesis. Pharmacol Ther, 103(2): 95–108

DOI

15
Devinsky O, Vezzani A, Najjar S, De Lanerolle N C, Rogawski M A (2013). Glia and epilepsy: excitability and inflammation. Trends Neurosci, 36(3): 174–184

DOI

16
DiMauro S, Hirano M, Kaufmann P, Tanji K, Sano M, Shungu D C, Bonilla E, DeVivo D C, (2002). Clinical features and genetics of myoclonic epilepsy with ragged red fibers. Adv Neurol, 89: 217–229

17
Dong K (2007). Insect sodium channels and insecticide resistance. Invert Neurosci, 7(1): 17–30

DOI

18
Engel J E, Wu C F (1994). Altered mechanoreceptor response in Drosophila bang-sensitive mutants. J Comp Physiol A Neuroethol Sens Neural Behav Physiol, 175(3): 267–278

DOI

19
Fahmy O G, Fahmy M J (1960). Cytogenetic analysis of the action of carcinogens and tumor inhibitors in Drosophila melanogaster. Genetics, 45: 419–438

20
Feng G, Deak P, Chopra M, Hall L M (1995). Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function. Cell, 82(6): 1001–1011

DOI

21
Fergestad T, Bostwick B, Ganetzky B (2006). Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics, 173(3): 1357–1364

DOI

22
Fertziger A P, Ranck J BJr (1970). Potassium accumulation in interstitial space during epileptiform seizures. Exp Neurol, 26(3): 571–585

DOI

23
Florence G, Dahlem M A, Almeida A C G, Bassani J W M, Kurths J (2009). The role of extracellular potassium dynamics in the different stages of ictal bursting and spreading depression: a computational study. J Theor Biol, 258(2): 219–228

DOI

24
Freeman A A, Syed S, Sanyal S (2013). Modeling the genetic basis for human sleep disorders in Drosophila. Commun Integr Biol, 6(1): e22733

DOI

25
Ganetzky B (1984). Genetic studies of membrane excitability in Drosophila: lethal interaction between two temperature-sensitive paralytic mutations. Genetics, 108: 897–911

26
Ganetzky B, Wu C F (1982a). Indirect suppression involving behavioral mutants with altered nerve excitability in Drosophila melanogaster. Genetics, 100: 597–614

27
Ganetzky B, Wu C F (1982b). Drosophila mutants with opposing effects on nerve excitability: genetic and spatial interactions in repetitive firing. J Neurophysiol, 47: 501–514

28
Glasscock E, Singhania A, Tanouye M A (2005). The mei-p26 gene encodes an RBCC-NHL protein that regulates seizure susceptibility in Drosophila. Genetics, 170: 1677–1689

DOI

29
Glasscock E, Tanouye M A (2005). Drosophila couch potato mutants exhibit complex neurological abnormalities including epilepsy phenotypes. Genetics, 169(4): 2137–2149

DOI

30
Goldin A L (2001). Resurgence of sodium channel research. Annu Rev Physiol, 63(1): 871–894

DOI

31
Greenhill S D, Jones R S G (2010). Diverse antiepileptic drugs increase the ratio of background synaptic inhibition to excitation and decrease neuronal excitability in neurons of the rat entorhinal cortex in vitro. Neurosci, 167(2): 456–474

DOI

32
Griesemer D A, Kellner C H, Beale M D, Smith G M (1997). Electroconvulsive therapy for treatment of intractable seizures: initial findings in two children. Neurology, 49(5): 1389–1392

DOI

33
Grigliatti T A, Hall L, Rosenbluth R, Suzuki D T (1973). Temperature-sensitive mutations in Drosophila melanogaster. Mol Gen Genet, 120(2): 107–114

DOI

34
Guo M (2012). Drosophila as a model to study mitochondrial dysfunction in Parkinson’s disease. Cold Spring Harb Perspect Med, 2(11): a009944

DOI

35
Hariharan I K, Haber D A (2003). Yeast, flies, worms, and fish in the study of human disease. N Engl J Med, 348(24): 2457–2463

DOI

36
Hebert S C, Mount D B, Gamba G (2004). Molecular physiology of cation-coupled Cl cotransport: the SLC12 family. Pflugers Arch, 447(5): 580–593

DOI

37
Hekmat-Scafe D S, Lundy M Y, Ranga R, Tanouye M A (2006). Mutations in the K+/Cl cotransporter gene kazachoc (kcc) increase seizure susceptibility in Drosophila. J Neurosci, 26(35): 8943–8954

DOI

38
Hekmat-Scafe D S, Mercado A, Fajilan A A, Lee A W, Hsu R, Mount D B, Tanouye M A (2010). Seizure sensitivity is ameliorated by targeted expression of K+-Cl cotransporter function in the mushroom body of the Drosophila brain. Genetics, 184(1): 171–183

DOI

39
Hirth F (2010). Drosophila melanogaster in the study of human neurodegeneration. CNS Neurol Disord Drug Targets, 9(4): 504–523

DOI

40
Howlett I C, Tanouye M A (2013). Seizure-sensitivity in Drosophila is ameliorated by dorsal vessel injection of the antiepileptic drug valproate. J Neurogenet, 27(4): 143–150

DOI

41
Hubner C A, Stein V, Hermans-Borgmeyer I, Meyer T, Ballanyi K, Jentsch T J (2001). Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron, 30(2): 515–524

DOI

42
Imbrici P, Jaffe S L, Eunson L H, Davies N P, Herd C, Robertson R, Kullmann D M, Hanna M G (2004). Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain, 127(12): 2682–2692

DOI

43
Jacobs J, Dubeau F, Olivier A, Andermann F (2008). Pathways of seizure propagation from the temporal to the occipital lobe. Epileptic Disord, 10: 266–270

44a
Kager H, Wadman W J, Somjen G G (2000). Simulated seizures and spreading depression in a neuron model incorporating interstitial space and ion concentrations. J Neurophysiol, 84(1): 195–512

44
Kandel E R, Spencer W A (1961). The pyramidal cell during hippocampal seizure. Epilepsia, 2(1): 63–69

DOI

45
Kawasaki F, Felling R, Ordway R W (2000). A temperature-sensitive paralytic mutant defines a primary synaptic calcium channel in Drosophila. J Neurosci, 20: 4885–4889

46
Kitamoto T (2001). Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. J Neurobiol, 47(2): 81–92

DOI

47
Koenig J H, Ikeda K (1989). Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval. J Neurosci, 9: 3844–3860

48
Kroll J R, Wong K G, Siddiqui F M, Tanouye M A (2015). Disruption of endocytosis with the dynamin mutant shibirets1 suppresses seizures in Drosophila. Genetics, 201(3): 1087–1102

DOI

49
Kuebler D, Tanouye M A (2000). Modifications of seizure susceptibility in Drosophila. J Neurophysiol, 83: 998–1009

50
Kuebler D, Tanouye M A (2002). The anticonvulsant sodium valproate reduces seizure-susceptibility in mutant Drosophila. Brain Res, 958(1): 36–42

DOI

51
Kuebler D, Zhang H, Ren X, Tanouye M A (2001). Genetic suppression of seizure susceptibility in Drosophila. J Neurophysiol, 86: 1211–1225

52
Kuromi H, Honda A, Kidokoro Y (2004). Ca2<?A3B2 h=-0.3h?>+ influx through distinct routes controls exocytosis and endocytosis at Drosophila presynaptic terminals. Neuron, 41(1): 101–111

DOI

53
Kwan P, Brodie M J (2000). Early identification of refractory epilepsy. N Engl J Med, 342(5): 314–319

DOI

54
Landmark C J (2008). Targets for antiepileptic drugs in the synapse. Med Sci Monit, 13: RA1–RA7

55
Lee J, Wu C F (2002). Electroconvulsive seizure behavior in Drosophila: analysis of the physiological repertoire underlying a stereotyped action pattern in bang sensitive mutants. J Neurosci, 22: 11065–11079

56
Lee J, Wu C F (2006). Genetic modifications of seizure susceptibility and expression by altered excitability in Drosophila Na(+) and K(+) channel mutants. J Neurophysiol, 96(5): 2465–2478

DOI

57
Lilly M, Carlson J (1990). smellblind: a gene required for Drosophila olfaction. Genetics, 124: 293–302

58
Lin W H, Baines R A (2014). Regulation of membrane excitability: a convergence on voltage-gated sodium conductance. Molec Neurobiol, 10.1007/s12035-014-8674-0 /fulltext.html

59
Lin W H, Wright D E, Muraro N I, Baines R A (2009). Alternative splicing in the voltage-gated sodium channel DmNav regulates activation, inactivation, and persistent current. J Neurophysiol, 102(3): 1994–2006

DOI

60
Loscher W (2002). Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs, 16: 669–694

DOI

61
Lossin C (2009). A catalog of SCN1A variants. Brain Dev, 31(2): 114–130

DOI

62
Loughney K, Kreber R, Ganetzky B (1989). Molecular analysis of the para locus, a sodium channel gene in Drosophila. Cell, 58(6): 1143–1154

DOI

63
Lunde M E, Lee E K, Rasmussen K G (2006). Electroconvulsive therapy in patients with epilepsy. Epilepsy Behav, 9(2): 355–359

DOI

64
Mayer F, Mayer N, Chinn L, Pinsonneault R L, Kroetz D, Bainton R J (2009). Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila. J Neurosci, 29(11): 3538–3550

DOI

65
McIntyre D C, Gilby K L (2008). Mapping seizure pathways in the temporal lobe. Epilepsia, 49(s3Suppl 3): 23–30

DOI

66
McNamara J O (1994). Cellular and molecular basis of epilepsy. J Neurosci, 14: 3413–3425

67
Mount D B, Delpire E, Gamba G, Hall A E, Poch E, Hoover R S, Herbert S C (1998). The electroneutral cation-chloride cotransporters. J Exp Biol, 201: 2091–2102

68
Mulley J C, Scheffer I E, Petrou S, Dibbens L M, Berkovic S F, Harkin L A (2005). SCN1A mutations and epilepsy. Hum Mutat, 25(6): 535–542

DOI

69
Noebels J L (1996). Targeting epilepsy genes. Neuron, 16(2): 241–244

DOI

70
O’Dowd D K, Gee J R, Smith M A (1995). Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons. J Neurosci, 15: 4005–4012

71
Oh C Y, Bainbridge J (2012). Lowering the seizure threshold associated with antidepressants, stimulants, antipsychotics, and others. Mental Health Clinician: November 2012-Epilepsy and seizure disorders and their treatment, Vol. 2, No. 5, pp. 127–128

72
Olson R O, Liu Z, Nomura Y, Song W, Dong K (2008). Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster. Insect Biochem Mol Biol, 38(5): 604–610

DOI

73
Paemka L, Mahajan V B, Ehaideb S N, Skeie J M, Tan M C, Wu S, Cox A J, Sowers L P, Gecz J, Jolly L, Ferguson P J, Darbro B, Schneider A, Scheffer I E, Carvill G L, Mefford H C, El-Shanti H, Wood S A, Manak J R, Bassuk A G (2015). Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase. PLoS Genet, 11(3): e1005022

DOI

74
Parker L, Padilla M, Du Y, Dong K, Tanouye M A (2011). Drosophila as a model for epilepsy: bss is a gain-of-function mutation in the Para sodium channel gene that leads to seizures. Genetics, 187(2): 523–534

DOI

75
Pavlidis P, Ramaswami M, Tanouye M A (1994). The Drosophila easily shocked gene: a mutation in a phospholipid synthetic pathway causes seizure, neuronal failure, and paralysis. Cell, 79(1): 23–33

DOI

76
Pavlidis P, Tanouye M A (1995). Seizures and failures in the giant fiber pathway of Drosophila bang-sensitive paralytic mutants. J Neurosci, 15: 5810–5819

77
Pfeiffer B D, Truman J W, Rubin G M (2012). Using translational enhancers to increase transgene expression in Drosophila. Proc Natl Acad Sci USA, 109(17): 6626–6631

DOI

78
Phelan P, Nakagawa M, Wilkin M B, Moffat K G, O’Kane C J, Davies J A, Bacon J P (1996). Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system. J Neurosci, 16: 1101–1113

79
Phelan P, Starich T A (2001). Innexins get into the gap. BioEssays, 23(5): 388–396

DOI

80
Phelan P, Stebbings L A, Baines R A, Bacon J P, Davies J A, Ford C (1998). Drosophila shaking-B protein forms gap junctions in paired Xenopus oocytes. Nature, 391(6663): 181–184

DOI

81
Pisani F, Oteri G, Costa C, Di Raimando G, Di Perri R (2002). Effects of psychotropic drugs on seizure threshold. Drug Saf, 25(2): 91–110

DOI

82
Pittendrigh B, Reenan R, ffrench-Constant R H, Ganetzky B (1997). Point mutations in the Drosophila sodium channel gene para associated with resistance to DDT and pyrethroid insecticides. Mol Gen Genet, 356(6): 602–610

DOI

83
Ramaswami M, Tanouye M A (1989). Two sodium channel genes in Drosophila: implications for channel diversity. Proc Natl Acad Sci USA, 86(6): 2079–2082

DOI

84
Read R (2011). Drosophila melanogaster as a model system for human brain cancers. Glia, 59(9): 1364–1376

DOI

85
Regenold W T, Weintraub D, Taller A (1998). Electroconvulsive therapy for epilepsy and major depression. Am J Geriatr Psychiatry, 6(2): 180–183(Top of Form)

DOI

86
Rein K, Zöckler M, Mader M T, Grübel C, Heisenberg M (2002). The Drosophila standard brain. Curr Biol, 12(3): 227–231

DOI

87
Reiter L T, Bier E (2001). Using Drosophila melanogaster to uncover human disease gene function and potential drug target proteins. Expert Opin Ther Targets, 6: 387–399

88
Reynolds E R, Stauffer E A, Feeney L, Rojahn E, Jacobs B, McKeever C (2003). Treatment with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants. J Neurobiol, 58(4): 503–513

DOI

89
Rieckhof G E, Yoshihara M, Guan Z, Littleton J T (2003). Presynaptic N-type calcium channels regulate synaptic growth. J Biol Chem, 278(42): 41099–41108

DOI

90
Royden C S, Pirrotta V, Jan L Y (1987). The tko locus, site of a behavioral mutation in D. melanogaster, codes for a protein homologous to prokaryotic ribosomal protein S12. Cell, 51(2): 165–173

DOI

91
Rusan Z M, Kingsford O A, Tanouye M A (2014). Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster. PLoS ONE, 9(6): e101117

DOI

92
Sackeim H A, Decina P, Prohovnik I, Malitz S S R, Resor S R (1987). Anticonvulsant and antidepressant properties of electroconvulsive therapy: a proposed mechanism of action. Biol Psychiatry, 18: 1301–1310

93
Salkoff L, Kelly L (1978). Temperature-induced seizure and frequency-dependent neuromuscular block in a ts mutant of Drosophila. Nature, 273(5658): 156–158

DOI

94
Saras A, Tanouye M A (2016). Mutations of the calcium channel gene cacophony suppress seizures in Drosophila. PLoS Genet, 12(1): e1005784

DOI

95
Schutte R J, Schutte S S, Algara J, Barragan E V, Gilligan J, Staber C, Savva Y A, Smith M A, Reenan R, O’Dowd D K (2014). Knock-in model of Dravet syndrome reveals a constitutive and conditional reduction in sodium current. J Neurophysiol, 112(4): 903–912

DOI

96
Schwarz N, Hahn A, Bast T, Müller S, Löffler H, Maljevic S, Gaily E, Prehl I, Biskup S, Joensuu T, Lehesjoki A E, Neubauer B A, Lerche H, Hedrich U B (2016). Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia. J Neurol, 263(2): 334–343

DOI

97
Sehgal A, Mignot E (2011). Genetics of sleep and sleep disorders. Cell, 146(2): 194–207

DOI

98
Seifert G, Carmignoto G, Steinhäuser C (2010). Astrocyte dysfunction in epilepsy. Brain Res Brain Res Rev, 63(1-2): 212–221

DOI

99
Shneker B F, Fountain N B (2003). Epilepsy. Dis Mon, 49(7): 426–478

DOI

100
Siddiqi O, Benzer S (1976). Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster. Proc Natl Acad Sci USA, 73(9): 3253–3257

DOI

101
Smith L A, Wang X, Peixoto A A, Neumann E K, Hall L M, Hall J C (1996). A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci, 16: 7868–7879

102
Somjen G G (2004). “Ions in the Brain : Normal Function, Seizures, and Stroke: Normal Function, Seizures, and Stroke”. Oxford University Press, USA. At<https://books.google.com/books?id=WjSoQVt-taYC&pgis=1>

103
Song J, Hu J, Tanouye M A (2007). Seizure suppression by top1 mutations in Drosophila. J Neurosci, 27(11): 2927–2937

DOI

104
Song J, Parker L, Hormozi L, Tanouye M A (2008). DNA topoisomerase I inhibitors ameliorate seizure-like behaviors and paralysis in a Drosophila model of epilepsy. Neuroscience, 156(3): 722–728

DOI

105
Song J, Tanouye M A (2006). Seizure suppression by shakB2, a gap junction mutation in Drosophila. J Neurophysiol, 95(2): 627–635

DOI

106
Song J, Tanouye M A (2007). Role for para sodium channel gene 3′ UTR in the modification of Drosophila seizure susceptibility. Dev Neurobiol, 67(14): 1944–1956

DOI

107
Stefan H, Lopes da Silva F H (2013). Epileptic neuronal networks: methods of identification and clinical relevance. Front Neurol, 4: 8

DOI

108
Steinhoff B, Hirsch E, Mutani R, Nakken K (2003). The ideal characteristics of antiepileptic therapy: an overview of old and new AEDs. Acta Neurol Scand, 107(2): 87–95

DOI

109
Stilwell G E, Saraswati S, Littleton J T, Chouinard S W (2006). Development of a Drosophila seizure model for in vivo high-throughput drug screening. Eur J Neurosci, 24(8): 2211–2222

DOI

110
Stödberg T, McTague A, Ruiz A J, Hirata H, Zhen J, Long P, Farabella I, Meyer E, Kawahara A, Vassallo G, Stivaros S M, Bjursell M K, Stranneheim H, Tigerschiöld S, Persson B, Bangash I, Das K, Hughes D, Lesko N, Lundeberg J, Scott R C, Poduri A, Scheffer I E, Smith H, Gissen P, Schorge S, Reith M E, Topf M, Kullmann D M, Harvey R J, Wedell A, Kurian M A (2015). Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. Nat Commun, 6: 8038

DOI

111
Stork T, Engelen D, Krudewig A, Silies M, Bainton R J, Klambt C (2008). Organization and function of the blood-brain barrier in Drosophila. J Neurosci, 28(3): 587–597

DOI

112
Sun L, Gilligan J, Staber C, Schutte R J, Nguyen V, O’Dowd D K, Reenan R (2012). A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure. J Neurosci, 32(41): 14145–14155

DOI

113
Suzuki D, Grigliatti T, Williamson R (1971). Temperature-sensitive mutations in Drosophila melanogaster, VII. A mutation (parats) causing reversible adult paralysis. Proc Natl Acad Sci USA, 68(5): 890–893

DOI

114
Tan J S, Lin F, Tanouye M A (2004). Potassium bromide, an anticonvulsant, is effective at alleviating seizures in the Drosophila bang-sensitive mutant bang senseless. Brain Res, 1020(1-2): 45–52

DOI

115
Tanouye M A, Ferrus A, Fujita S C (1981). Abnormal action potentials associated with the Shaker complex locus of Drosophila. Proc Natl Acad Sci USA, 78(10): 6548–6552

DOI

116
Tao H, Manak J R, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh N S, Yang T, Wu S, Chen S, Fox M H, Gurnett C, Montine T, Bird T, Shaffer L G, Rosenfeld J A, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto R P, Scott M P, Antic D, Reed J, Boland R, Ehaideb S N, El-Shanti H, Mahajan V B, Ferguson P J, Axelrod J D, Lehesjoki A E, Fritzsch B, Slusarski D C, Wemmie J, Ueno N, Bassuk A G (2011). Mutations in Prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet, 88(2): 138–149

DOI

117
Thackeray J R, Ganetzky B (1994). Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms. J Neurosci, 14: 2569–2578

118
Thackeray J R, Ganetzky B (1995). Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para. Genetics, 141: 203–214

119
Tornberg J, Voikar V, Savilahti H, Rauvala H, Airaksinen M S (2005). Behavioural phenotypes of hypomorphic KCC2-deficient mice. Eur J Neurosci, 21(5): 1327–1337

DOI

120
Ueda A, Grabbe C, Lee J, Lee J, Palmer R H, Wu C F (2008). Mutation of Drosophila focal adhesion kinase induces bang-sensitive behavior and disrupts glial function, axonal conduction and synaptic transmission. Eur J Neurosci, 27(11): 2860–2870

DOI

121
van der Bliek A M, Meyerowitz E M (1991). Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature, 351(6325): 411–414

DOI

122
Warmke J W, Reenan R A G, Wang P, Qian S, Arena J P, Wang J, Wunderler D, Liu K, Kaczorowski G J, Ploeg L H T V, Ganetzky B, Cohen C J (1997). Functional expression of Drosophila para sodium channels: modulation by the membrane protein tipE and toxin pharmacology. J Gen Physiol, 110(2): 119–133

DOI

123
Watanabe T K, Yamazaki T (1976). Evidence for coadaptation: negative correlation between lethal genes and polymorphic inversions in Drosophila melanogaster. Genetics, 82: 697–702

124
White H S, Smith M D, Wilcox K S (2007). Mechanisms of action of antiepileptic drugs. Int Rev Neurobiol, 81: 85–110

DOI

125
Willoughby L, Chang H, Lumb C, Robin C, Batterham P, Daborn P J (2006). A comparison of Drosophila melanogaster detoxification gene induction responses for six insecticides, caffeine and Phenobarbital. Insect Biochem Mol Biol, 36(12): 934–942

DOI

126
Woo N S, Lu J, England R, McClellan R, Dufour S, Mount D B, Deutch A Y, Lovinger D M, Delpire E (2002). Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene. Hippocampus, 12(2): 258–268

DOI

127
Wu C F, Ganetzky B (1980). Genetic alteration of nerve membrane excitability in temperature-sensitive paralytic mutants of Drosophila melanogaster. Nature, 286(5775): 814–816

DOI

128
Zhang H, Tan J, Reynolds E, Kuebler D, Faulhaber S, Tanouye M A (2002). The Drosophila slamdance gene: a mutation in an aminopeptidase can cause seizure, paralysis and neuronal failure. Genetics, 162: 1283–1299

129
Zhang Y Q, Roote J, Brogna S, Davis A W, Barbash D A, Nash D, Ashburner M (1999). Stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster. Genetics, 153: 891–903

130
Zuckermann E C, Glaser G H (1970). Activation of experimental epileptogenic foci. Action of increased K+ in extracellular spaces of the brain. Arch Neurol, 23(4): 358–364

DOI

Outlines

/