Drosophila seizure disorders: genetic suppression of seizure susceptibility
Received date: 15 Feb 2016
Accepted date: 24 Mar 2016
Published date: 17 May 2016
Copyright
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.
Key words: Drosophila; epilepsy; seizure disorders; sodium channel; seizure-suppressor genes
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
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
|
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
|
4 |
Benzer S (1971). From the gene to behavior. JAMA, 218(7): 1015–1022
|
5 |
Boettger T, Rust M B, Maier H, Seidenbecher T, Schweizer M, Keating D J, Faulhaber J, Ehmke H, Pfeffer C, Scheel O,
|
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
|
8 |
Catterall W A (2014). Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu Rev Pharmacol Toxicol, 54(1): 317–338
|
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
|
10 |
Champoux J J (2001). DNA topoisomerases: Structure, function and mechanism. Annu Rev Biochem, 70(1): 369–413
|
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
|
12 |
Chvatal A, Sykova E (2000). Glial influence on neuronal signaling. Prog Brain Res, 125: 199–216
|
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
|
14 |
D'Ambrosio R (2004). The role of glial membrane ion channels in seizures and epileptogenesis. Pharmacol Ther, 103(2): 95–108
|
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
|
16 |
DiMauro S, Hirano M, Kaufmann P, Tanji K, Sano M, Shungu D C, Bonilla E, DeVivo D C,
|
17 |
Dong K (2007). Insect sodium channels and insecticide resistance. Invert Neurosci, 7(1): 17–30
|
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
|
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
|
21 |
Fergestad T, Bostwick B, Ganetzky B (2006). Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics, 173(3): 1357–1364
|
22 |
Fertziger A P, Ranck J BJr (1970). Potassium accumulation in interstitial space during epileptiform seizures. Exp Neurol, 26(3): 571–585
|
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
|
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
|
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
|
29 |
Glasscock E, Tanouye M A (2005). Drosophila couch potato mutants exhibit complex neurological abnormalities including epilepsy phenotypes. Genetics, 169(4): 2137–2149
|
30 |
Goldin A L (2001). Resurgence of sodium channel research. Annu Rev Physiol, 63(1): 871–894
|
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
|
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
|
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
|
34 |
Guo M (2012). Drosophila as a model to study mitochondrial dysfunction in Parkinson’s disease. Cold Spring Harb Perspect Med, 2(11): a009944
|
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
|
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
|
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
|
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
|
39 |
Hirth F (2010). Drosophila melanogaster in the study of human neurodegeneration. CNS Neurol Disord Drug Targets, 9(4): 504–523
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
53 |
Kwan P, Brodie M J (2000). Early identification of refractory epilepsy. N Engl J Med, 342(5): 314–319
|
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
|
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
|
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
|
61 |
Lossin C (2009). A catalog of SCN1A variants. Brain Dev, 31(2): 114–130
|
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
|
63 |
Lunde M E, Lee E K, Rasmussen K G (2006). Electroconvulsive therapy in patients with epilepsy. Epilepsy Behav, 9(2): 355–359
|
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
|
65 |
McIntyre D C, Gilby K L (2008). Mapping seizure pathways in the temporal lobe. Epilepsia, 49(s3Suppl 3): 23–30
|
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
|
69 |
Noebels J L (1996). Targeting epilepsy genes. Neuron, 16(2): 241–244
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
84 |
Read R (2011). Drosophila melanogaster as a model system for human brain cancers. Glia, 59(9): 1364–1376
|
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)
|
86 |
Rein K, Zöckler M, Mader M T, Grübel C, Heisenberg M (2002). The Drosophila standard brain. Curr Biol, 12(3): 227–231
|
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
|
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
|
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
|
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
|
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
|
94 |
Saras A, Tanouye M A (2016). Mutations of the calcium channel gene cacophony suppress seizures in Drosophila. PLoS Genet, 12(1): e1005784
|
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
|
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
|
97 |
Sehgal A, Mignot E (2011). Genetics of sleep and sleep disorders. Cell, 146(2): 194–207
|
98 |
Seifert G, Carmignoto G, Steinhäuser C (2010). Astrocyte dysfunction in epilepsy. Brain Res Brain Res Rev, 63(1-2): 212–221
|
99 |
Shneker B F, Fountain N B (2003). Epilepsy. Dis Mon, 49(7): 426–478
|
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
|
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
|
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
|
105 |
Song J, Tanouye M A (2006). Seizure suppression by shakB2, a gap junction mutation in Drosophila. J Neurophysiol, 95(2): 627–635
|
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
|
107 |
Stefan H, Lopes da Silva F H (2013). Epileptic neuronal networks: methods of identification and clinical relevance. Front Neurol, 4: 8
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
/
〈 | 〉 |