title: Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex.
abstract: One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319. It is not known whether reduced expression of KIAA0319 can degrade the brain's ability to process phonemes. In the current study, we used RNA interference (RNAi) to reduce expression of Kiaa0319 (the rat homolog of the human gene KIAA0319) and evaluate the effect in a rat model of phoneme discrimination. Speech discrimination thresholds in normal rats are nearly identical to human thresholds. We recorded multiunit neural responses to isolated speech sounds in primary auditory cortex (A1) of rats that received in utero RNAi of Kiaa0319. Reduced expression of Kiaa0319 increased the trial-by-trial variability of speech responses and reduced the neural discrimination ability of speech sounds. Intracellular recordings from affected neurons revealed that reduced expression of Kiaa0319 increased neural excitability and input resistance. These results provide the first evidence that decreased expression of the dyslexia-associated gene Kiaa0319 can alter cortical responses and impair phoneme processing in auditory cortex.
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas.
authors: T M
authors: TM
authors: Centanni
authors: University of Connecticut.
authors: A B
authors: AB
authors: Booker
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas.
authors: A M
authors: AM
authors: Sloan
authors: University of Connecticut.
authors: F
authors: F
authors: Chen
authors: University of Connecticut.
authors: B J
authors: BJ
authors: Maher
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas.
authors: R S
authors: RS
authors: Carraway
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas.
authors: N
authors: N
authors: Khodaparast
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas.
authors: R
authors: R
authors: Rennaker
authors: University of Connecticut.
authors: J J
authors: JJ
authors: LoTurco
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas.
authors: M P
authors: MP
authors: Kilgard
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D004410:Dyslexia / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011930:Reaction Time / Q000235:genetics; D014851:Wakefulness
chemical_list: D015815:Cell Adhesion Molecules; C582196:RGD1307443 protein, rat; D034741:RNA, Small Interfering
keywords: reading; specific language impairment; temporal processing; timing
references: Nat Rev Neurosci. 2002 Oct;3(10):767-80
references: 12360321
references: Behav Brain Res. 2011 May 16;219(1):68-74
references: 21167211
references: Ear Hear. 1996 Aug;17(4):314-26
references: 8862969
references: Cereb Cortex. 2013 Mar;23(3):670-83
references: 22426334
references: JAMA. 1991 Sep 18;266(11):1527-34
references: 1880884
references: Sci Am. 1985 Jan;252(1):46-52
references: 3964957
references: Histol Histopathol. 2011 Aug;26(8):953-63
references: 21692029
references: Biol Psychiatry. 2011 Aug 1;70(3):237-45
references: 21457949
references: J Neurosci. 2012 Jan 18;32(3):966-71
references: 22262894
references: J Exp Child Psychol. 1997 Aug;66(2):211-35
references: 9245476
references: Physiol Behav. 2010 Sep 1;101(2):260-8
references: 20580729
references: Nature. 1997 May 8;387(6629):176-8
references: 9144287
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6832-7
references: 10841578
references: Lancet. 2012 May 26;379(9830):1997-2007
references: 22513218
references: Proc Natl Acad Sci U S A. 1999 May 25;96(11):6483-8
references: 10339614
references: Hear Res. 2012 Jul;289(1-2):1-12
references: 22575207
references: Eur J Neurosci. 2011 Dec;34(11):1823-38
references: 22098331
references: Behav Brain Res. 2005 Jan 6;156(1):95-103
references: 15474654
references: Neuropsychologia. 1974 Jan;12(1):83-93
references: 4821193
references: Neuroscience. 2008 Mar 27;152(3):723-33
references: 18313856
references: Proc Biol Sci. 1996 Aug 22;263(1373):961-5
references: 8805833
references: Brain Res. 2010 Jun 4;1335:53-62
references: 20381471
references: Neuron. 2011 Dec 22;72(6):1080-90
references: 22196341
references: Mol Psychiatry. 2008 Jul;13(7):729-40
references: 17684495
references: J Neurosci. 2012 Jan 18;32(3):817-25
references: 22262880
references: Ear Hear. 2012 Jan-Feb;33(1):134-43
references: 21844810
references: Am J Hum Genet. 2004 Dec;75(6):1046-58
references: 15514892
references: Nat Neurosci. 2003 Dec;6(12):1277-83
references: 14625554
references: Brain Res Bull. 2007 Mar 15;71(5):508-14
references: 17259020
references: Ann Dyslexia. 1986 Jan;36(1):103-17
references: 24243454
references: Int J Lang Commun Disord. 2002 Jul-Sep;37(3):289-308
references: 12201979
references: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10389-94
references: 20498069
references: J Neurosci Methods. 2005 Mar 15;142(1):97-105
references: 15652622
references: Behav Genet. 2011 Jan;41(1):50-7
references: 20949370
references: Brain. 2010 Mar;133(Pt 3):868-79
references: 20061325
references: Pro Fono. 2010 Oct-Dec;22(4):537-42
references: 21271113
references: Brain Lang. 1980 Mar;9(2):182-98
references: 7363063
references: Hum Genet. 2004 Jul;115(2):128-38
references: 15138886
references: Biol Psychiatry. 2012 Oct 15;72(8):671-6
references: 22683091
references: Brain Cogn. 2001 Jun-Jul;46(1-2):104-8
references: 11527306
references: Hum Mol Genet. 2006 May 15;15(10):1659-66
references: 16600991
references: Nat Neurosci. 2008 May;11(5):603-8
references: 18425123
references: Science. 1994 Oct 14;266(5183):276-9
references: 7939663
references: N Engl J Med. 1992 Jan 16;326(3):145-50
references: 1727544
references: Neuron. 2009 Nov 12;64(3):311-9
references: 19914180
references: Brain. 1996 Feb;119 ( Pt 1):143-57
references: 8624677
references: Science. 1996 Aug 16;273(5277):971-3
references: 8688085
references: Dev Sci. 2009 Sep;12(5):732-45
references: 19702766
references: Dev Neurosci. 2008;30(1-3):144-56
references: 18075262
references: Int J Psychophysiol. 2001 Feb;40(1):77-87
references: 11166109
references: J Biol Chem. 2010 Dec 17;285(51):40148-62
references: 20943657
references: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2860-5
references: 12604786
references: Can J Psychol. 1987 Mar;41(1):48-61
references: 3502888
references: Clin Neurophysiol. 2002 Apr;113(4):485-94
references: 11955993
references: Nat Neurosci. 2006 Oct;9(10):1213-7
references: 17001339
references: Psychophysiology. 2000 Mar;37(2):262-6
references: 10731777
references: Cereb Cortex. 2010 Apr;20(4):884-97
references: 19679544
references: Hum Mol Genet. 2008 Mar 15;17(6):859-71
references: 18063668
references: Neurosci Lett. 1999 Aug 27;271(3):202-4
references: 10507704
references: Restor Neurol Neurosci. 2007;25(3-4):295-310
references: 17943007
references: Neuroreport. 2001 Feb 12;12(2):299-307
references: 11209939
references: Am J Hum Genet. 2005 Apr;76(4):581-91
references: 15717286
references: J Speech Lang Hear Res. 2000 Dec;43(6):1367-79
references: 11193958
references: N Engl J Med. 1991 Jul 25;325(4):231-7
references: 2057024
references: Arch Neurol. 1992 May;49(5):527-34
references: 1580816
references: Mol Psychiatry. 2006 Dec;11(12):1085-91, 1061
references: 17033633
references: Brain Res. 2012 Apr 11;1448:42-55
references: 22364735
references: J Neurosci Methods. 2004 May 30;135(1-2):107-20
references: 15020095
references: Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13841-6
references: 22869724
references: Int J Dev Neurosci. 2012 Jun;30(4):293-302
references: 22326444
references: J Speech Lang Hear Res. 2002 Jun;45(3):564-72
references: 12069008
references: J Neurosci Methods. 2005 Mar 30;142(2):169-76
references: 15698656
references: J Neural Eng. 2007 Jun;4(2):L1-5
references: 17409469
references: J Assoc Res Otolaryngol. 2012 Aug;13(4):527-42
references: 22549175
references: PLoS Genet. 2009 Mar;5(3):e1000436
references: 19325871
references: J Exp Psychol Hum Percept Perform. 2011 Dec;37(6):1957-75
references: 21823808
references: Mol Psychiatry. 2011 Jan;16(1):97-107
references: 19786962
references: Biol Psychiatry. 2007 Oct 1;62(7):811-7
references: 17597587
references: Am J Hum Genet. 2006 Jan;78(1):52-62
references: 16385449
references: Arch Neurol. 1991 Jun;48(6):637-43
references: 2039387
references: JAMA. 1990 Aug 22-29;264(8):998-1002
references: 2376893
references: Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16865-70
references: 19805387
references: J Learn Disabil. 1999 Mar-Apr;32(2):138-48
references: 15499714
references: Brain. 2003 Apr;126(Pt 4):841-65
references: 12615643
references: Cell Mol Neurobiol. 2011 Jan;31(1):27-35
references: 20697954
references: Brain. 1997 May;120 ( Pt 5):739-59
references: 9183247
references: Eur Child Adolesc Psychiatry. 1999;8 Suppl 3:56-9
references: 10638372