title: Behavioral and synaptic circuit features in a zebrafish model of fragile X syndrome.
abstract: Fragile X syndrome (FXS) is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl) and medial (Dm) division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Ming-Chong
authors.initials: MC
authors.lastname: Ng
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Kwok-Tung
authors.initials: KT
authors.lastname: Lu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001007:Anxiety; D001362:Avoidance Learning; D001522:Behavior, Animal; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D055786:Gene Knockout Techniques; D005838:Genotype; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D010641:Phenotype; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1
references.citation: Biol Cybern. 1990;64(1):33-9
references.pmid: 2149518
references.citation: Neuroscience. 1983 Dec;10(4):1051-69
references.pmid: 6141538
references.citation: Nat Genet. 1999 May;22(1):98-101
references.pmid: 10319871
references.citation: J Neurobiol. 2006 Apr;66(5):463-75
references.pmid: 16470869
references.citation: J Neurosci Res. 2011 Feb;89(2):176-82
references.pmid: 21162125
references.citation: Rev Neurosci. 2011;22(1):107-19
references.pmid: 21615265
references.citation: Nature. 1995 Sep 14;377(6545):115-8
references.pmid: 7675078
references.citation: Science. 1991 May 24;252(5009):1097-102
references.pmid: 2031184
references.citation: Fish Physiol Biochem. 2012 Aug;38(4):1099-1106
references.pmid: 22215143
references.citation: Nat Genet. 1993 Aug;4(4):335-40
references.pmid: 8401578
references.citation: Neurobiol Learn Mem. 2009 Nov;92(4):529-34
references.pmid: 19591953
references.citation: Cell. 1994 Jul 15;78(1):23-33
references.pmid: 8033209
references.citation: J Neurosci. 2005 Aug 10;25(32):7385-92
references.pmid: 16093389
references.citation: Nat Genet. 1993 Jun;4(2):147-53
references.pmid: 8348153
references.citation: Mol Cell Neurosci. 2008 Apr;37(4):747-60
references.pmid: 18280750
references.citation: Am J Med Genet. 1991 Dec 1;41(3):289-94
references.pmid: 1724112
references.citation: J Neurosci. 1995 Nov;15(11):7548-64
references.pmid: 7472506
references.citation: Neurobiol Dis. 2009 Nov;36(2):361-73
references.pmid: 19666116
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7746-50
references.pmid: 12032354
references.citation: J Neurosci. 2008 Jul 30;28(31):7847-62
references.pmid: 18667617
references.citation: Science. 2007 Nov 16;318(5853):1144-6
references.pmid: 18006748
references.citation: Dev Genes Evol. 2005 Apr;215(4):198-206
references.pmid: 15818485
references.citation: Am J Med Genet. 1996 Jul 12;64(1):196-7
references.pmid: 8826475
references.citation: Science. 2008 Oct 10;322(5899):176
references.pmid: 18845717
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5401-4
references.pmid: 9144249
references.citation: Int J Neuropsychopharmacol. 2011 Jun;14(5):618-30
references.pmid: 20497624
references.citation: Anat Embryol (Berl). 1996 Aug;194(2):187-203
references.pmid: 8827327
references.citation: Mol Cell Neurosci. 2002 Feb;19(2):138-51
references.pmid: 11860268
references.citation: Neurosci Lett. 2004 Nov 11;370(2-3):248-51
references.pmid: 15488332
references.citation: J Neurochem. 2009 Nov;111(3):635-46
references.pmid: 19659572
references.citation: Nat Genet. 1993 Jan;3(1):36-43
references.pmid: 8490651
references.citation: Nature. 1993 Jan 7;361(6407):31-9
references.pmid: 8421494
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15537-42
references.pmid: 17881561
references.citation: J Neurosci. 2010 Mar 31;30(13):4590-600
references.pmid: 20357110
references.citation: Neuron. 2008 Oct 23;60(2):201-14
references.pmid: 18957214
references.citation: Neurochem Res. 2012 Jul;37(7):1545-53
references.pmid: 22437435
references.citation: Curr Opin Genet Dev. 2006 Jun;16(3):270-5
references.pmid: 16647847
references.citation: Hum Mol Genet. 2000 May 1;9(8):1145-59
references.pmid: 10767339
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2454-9
references.pmid: 17287348
references.citation: PLoS One. 2009 Nov 19;4(11):e7910
references.pmid: 19936290
references.citation: Hum Mol Genet. 1992 Sep;1(6):397-400
references.pmid: 1301913
references.citation: J Neurophysiol. 2006 May;95(5):3291-5
references.pmid: 16452252
references.citation: Neurosci Res. 2010 Jun;67(2):156-61
references.pmid: 20298728
references.citation: Child Adolesc Psychiatr Clin N Am. 2007 Jul;16(3):663-75
references.pmid: 17562585
references.citation: J Neurophysiol. 2009 May;101(5):2572-80
references.pmid: 19244359
references.citation: Brain Res Bull. 2002 Feb-Mar 1;57(3-4):397-9
references.pmid: 11922997
references.citation: Neurosci Lett. 2012 Mar 23;512(2):109-13
references.pmid: 22342305
references.citation: Neuropsychopharmacology. 2009 Mar;34(4):1011-26
references.pmid: 18843266
references.citation: Cell. 1991 Dec 20;67(6):1047-58
references.pmid: 1760838
references.citation: Eur J Neurosci. 2011 Apr;33(7):1252-5
references.pmid: 21375600
references.citation: Nature. 1981 May 28;291(5813):293-6
references.pmid: 7248006
references.citation: Genes Dev. 2005 Jun 1;19(11):1288-93
references.pmid: 15937218
references.citation: J Neurosci. 2004 Mar 3;24(9):2335-42
references.pmid: 14999085
references.citation: Cell. 1991 May 31;65(5):905-14
references.pmid: 1710175
references.citation: Genes Brain Behav. 2012 Jul;11(5):586-600
references.pmid: 22405502