title: Long-lasting neural circuit dysfunction following developmental ethanol exposure.
abstract: Fetal Alcohol Spectrum Disorder (FASD) is a general diagnosis for those exhibiting long-lasting neurobehavioral and cognitive deficiencies as a result of fetal alcohol exposure. It is among the most common causes of mental deficits today. Those impacted are left to rely on advances in our understanding of the nature of early alcohol-induced disorders toward human therapies. Research findings over the last decade have developed a model where ethanol-induced neurodegeneration impacts early neural circuit development, thereby perpetuating subsequent integration and plasticity in vulnerable brain regions. Here we review our current knowledge of FASD neuropathology based on discoveries of long-lasting neurophysiological effects of acute developmental ethanol exposure in animal models. We discuss the important balance between synaptic excitation and inhibition in normal neural network function, and relate the significance of that balance to human FASD as well as related disease states. Finally, we postulate that excitation/inhibition imbalance caused by early ethanol-induced neurodegeneration results in perturbed local and regional network signaling and therefore neurobehavioral pathology.
authors.affiliation: Department of Child and Adolescent Psychiatry, New York University Langone School of Medicine, One Park Avenue, Eighth Floor, New York, NY 10128, USA ; Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sadrian
authors.forename: Donald A
authors.initials: DA
authors.lastname: Wilson
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
keywords: FASD; alcohol; brain development; excitation/inhibition balance; neural circuit; neurodegeneration
references.citation: Horm Behav. 2010 Nov;58(5):835-43
references.pmid: 20736015
references.citation: Nature. 2012 Sep 20;489(7416):385-90
references.pmid: 22914087
references.citation: Neurotoxicol Teratol. 1999 May-Jun;21(3):285-91
references.pmid: 10386832
references.citation: J Neurosci. 2011 Nov 2;31(44):15962-71
references.pmid: 22049439
references.citation: Neuropsychopharmacology. 2011 Jan;36(1):316-38
references.pmid: 20844478
references.citation: J Pediatr. 1978 Jan;92(1):64-7
references.pmid: 619080
references.citation: Neuroscience. 2005;136(1):269-79
references.pmid: 16181739
references.citation: Addict Biol. 2004 Jun;9(2):137-49; discussion 151
references.pmid: 15223539
references.citation: Alcohol Clin Exp Res. 2007 Apr;31(4):665-74
references.pmid: 17374046
references.citation: MMWR Morb Mortal Wkly Rep. 2003 May 16;52(19):441-4
references.pmid: 12807086
references.citation: J Neurodev Disord. 2012 Jul 03;4(1):18
references.pmid: 22958715
references.citation: J Neurosci. 2010 Nov 10;30(45):14964-71
references.pmid: 21068299
references.citation: Alcohol. 2000 May;21(1):49-57
references.pmid: 10946157
references.citation: Teratology. 1988 Mar;37(3):223-31
references.pmid: 3368876
references.citation: Neurobiol Dis. 2004 Dec;17(3):403-14
references.pmid: 15571976
references.citation: Brain Res. 1990 Dec 24;537(1-2):109-14
references.pmid: 1982237
references.citation: Schizophr Res. 2005 Jan 1;72(2-3):109-22
references.pmid: 15560956
references.citation: Alcohol Clin Exp Res. 2010 Jun;34(6):1084-9
references.pmid: 20374205
references.citation: Hippocampus. 2000;10(1):94-110
references.pmid: 10706221
references.citation: Int J Epidemiol. 2011 Apr;40(2):278-82
references.pmid: 21450683
references.citation: Front Mol Neurosci. 2008 Apr 08;1:6
references.pmid: 18946539
references.citation: Alcohol Clin Exp Res. 2010 Jun;34(6):1022-32
references.pmid: 20374212
references.citation: Alcohol. 1986 Mar-Apr;3(2):107-12
references.pmid: 2941034
references.citation: Nat Rev Neurosci. 2007 Jan;8(1):45-56
references.pmid: 17180162
references.citation: Alcohol Clin Exp Res. 2011 May;35(5):849-61
references.pmid: 21303384
references.citation: Neuropsychol Rev. 2011 Jun;21(2):133-47
references.pmid: 21347880
references.citation: Behav Brain Res. 2010 Jul 11;210(2):164-70
references.pmid: 20170688
references.citation: Alcohol Clin Exp Res. 2006 Oct;30(10):1799-806
references.pmid: 17010147
references.citation: Brain Res. 2004 Nov 26;1028(1):66-74
references.pmid: 15518643
references.citation: Neuropsychol Rev. 2011 Jun;21(2):167-85
references.pmid: 21445552
references.citation: Neurotoxicol Teratol. 2003 Nov-Dec;25(6):681-8
references.pmid: 14624967
references.citation: Brain Res. 2008 Apr 14;1204:16-23
references.pmid: 18329634
references.citation: Alcohol Clin Exp Res. 1997 Nov;21(8):1418-28
references.pmid: 9394113
references.citation: Biol Psychiatry. 2012 Sep 1;72(5):378-88
references.pmid: 22622000
references.citation: Neurochem Res. 2010 Apr;35(4):651-9
references.pmid: 20049527
references.citation: Science. 1989 Mar 31;243(4899):1721-4
references.pmid: 2467382
references.citation: Genome Med. 2010 Apr 28;2(4):27
references.pmid: 20423530
references.citation: Alcohol Alcohol. 1994 Jul;29(4):385-95
references.pmid: 7986275
references.citation: Alcohol Clin Exp Res. 2013 Mar;37(3):425-34
references.pmid: 23347220
references.citation: J Neurosci. 2010 Feb 17;30(7):2513-20
references.pmid: 20164336
references.citation: Child Neuropsychol. 2013;19(6):579-87
references.pmid: 23030694
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):E2895-903
references.pmid: 22869752
references.citation: Alcohol. 2010 May;44(3):283-90
references.pmid: 20488644
references.citation: Nat Rev Neurosci. 2005 Nov;6(11):877-88
references.pmid: 16261181
references.citation: Biochem Biophys Res Commun. 2008 Mar 14;367(3):597-602
references.pmid: 18190791
references.citation: J Subst Abuse Treat. 2005 Oct;29(3):173-80
references.pmid: 16183466
references.citation: Int J Dev Neurosci. 2012 Aug;30(5):351-7
references.pmid: 22617459
references.citation: Brain Res Dev Brain Res. 2003 May 14;142(2):223-7
references.pmid: 12711375
references.citation: Am J Med Genet C Semin Med Genet. 2007 Aug 15;145C(3):261-72
references.pmid: 17640043
references.citation: Alcohol Clin Exp Res. 1999 Apr;23(4):726-34
references.pmid: 10235310
references.citation: Alcohol. 1999 Feb;17(2):163-8
references.pmid: 10064385
references.citation: Annu Rev Nurs Res. 2005;23:101-34
references.pmid: 16350764
references.citation: Neuroscience. 2012 Mar 29;206:122-35
references.pmid: 22266347
references.citation: Mol Brain. 2011 Jul 07;4:29
references.pmid: 21736737
references.citation: Alcohol Alcohol. 2009 Mar-Apr;44(2):108-14
references.pmid: 19147799
references.citation: Biochem Biophys Res Commun. 2006 Dec 1;350(4):905-10
references.pmid: 17045245
references.citation: Brain Res Dev Brain Res. 2002 Feb 28;133(2):115-26
references.pmid: 11882342
references.citation: Nat Med. 2011 May;17(5):566-72
references.pmid: 21499268
references.citation: Alcohol. 2004 Oct-Nov;34(2-3):187-96
references.pmid: 15902912
references.citation: J Chem Neuroanat. 2005 Oct;30(2-3):144-57
references.pmid: 16122904
references.citation: Lancet. 1973 Nov 3;302(7836):999-1001
references.pmid: 4127281
references.citation: Alcohol Clin Exp Res. 1990 Dec;14(6):813-8
references.pmid: 2088116
references.citation: Alcohol Clin Exp Res. 2013 Jan;37(1):132-40
references.pmid: 23072431
references.citation: Pharmacol Biochem Behav. 1996 Dec;55(4):489-99
references.pmid: 8981579
references.citation: Neurochem Int. 1997 Nov;31(5):659-76
references.pmid: 9364452
references.citation: Early Hum Dev. 1979 Mar;3(1):79-83
references.pmid: 118862
references.citation: Alcohol. 2012 Sep;46(6):603-12
references.pmid: 22572057
references.citation: Alcohol Res Health. 2001;25(3):159-67
references.pmid: 11810953
references.citation: Am J Med Genet C Semin Med Genet. 2004 May 15;127C(1):42-50
references.pmid: 15095471
references.citation: Alcohol Clin Exp Res. 1990 Feb;14(1):107-18
references.pmid: 1689970
references.citation: J Autism Dev Disord. 2008 May;38(5):867-75
references.pmid: 17899349
references.citation: J Neurosci. 2005 Aug 10;25(32):7317-23
references.pmid: 16093381
references.citation: Biol Psychiatry. 2010 Apr 1;67(7):672-8
references.pmid: 19880095
references.citation: J Pers Assess. 2007 Aug;89(1):30-40
references.pmid: 17604532
references.citation: Alcohol Clin Exp Res. 1979 Apr;3(2):99-106
references.pmid: 391081
references.citation: Brain Res Dev Brain Res. 2002 Dec 15;139(2):295-9
references.pmid: 12480144
references.citation: Behav Brain Res. 2011 Oct 1;223(2):376-87
references.pmid: 21601595
references.citation: J Neurophysiol. 2001 Dec;86(6):2823-33
references.pmid: 11731539
references.citation: Exp Biol Med (Maywood). 2005 Jun;230(6):357-65
references.pmid: 15956765
references.citation: Science. 2011 Sep 2;333(6047):1262-6
references.pmid: 21885776
references.citation: Trends Cogn Sci. 2011 Dec;15(12):592-600
references.pmid: 22055387
references.citation: J Neurochem. 1992 Dec;59(6):2193-200
references.pmid: 1431900
references.citation: J Child Psychol Psychiatry. 2007 Nov;48(11):1111-21
references.pmid: 17995487
references.citation: Synapse. 2010 Feb;64(2):127-35
references.pmid: 19771589
references.citation: J Neurosci. 2004 Feb 4;24(5):1182-9
references.pmid: 14762136
references.citation: J Neurosci Res. 2003 Nov 15;74(4):577-88
references.pmid: 14598302
references.citation: Alcohol Clin Exp Res. 2007 Dec;31(12):2073-82
references.pmid: 17949464
references.citation: Front Neurosci. 2010 Jun 28;4:41
references.pmid: 20661453
references.citation: Alcohol Alcohol. 1998 Jul-Aug;33(4):417-20
references.pmid: 9719401
references.citation: Exp Biol Med (Maywood). 2005 Jun;230(6):389-93
references.pmid: 15956768
references.citation: Neurobiol Dis. 2002 Mar;9(2):205-19
references.pmid: 11895372
references.citation: Brain Res Rev. 2010 Sep 24;64(2):283-303
references.pmid: 20471420
references.citation: Neuropharmacology. 2009 Feb;56(2):541-55
references.pmid: 19027758
references.citation: Phys Occup Ther Pediatr. 2008 May;28(2):117-36
references.pmid: 18846892
references.citation: Alcohol Clin Exp Res. 2011 Nov;35(11):1974-84
references.pmid: 21649667
references.citation: Front Hum Neurosci. 2010 Dec 21;4:224
references.pmid: 21191475
references.citation: Alcohol Clin Exp Res. 2000 May;24(5):706-15
references.pmid: 10832913
references.citation: J Stud Alcohol Drugs. 2011 Jul;72(4):530-5
references.pmid: 21683034
references.citation: Cell. 2012 Apr 27;149(3):708-21
references.pmid: 22541439
references.citation: Front Mol Neurosci. 2008 Mar 28;1:2
references.pmid: 18946535
references.citation: Neurobiol Dis. 2006 Jun;22(3):548-54
references.pmid: 16459096
references.citation: J Biomed Sci. 2010 Aug 24;17 Suppl 1:S12
references.pmid: 20804586
references.citation: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8740-5
references.pmid: 22592800
references.citation: Alcohol Clin Exp Res. 1997 Aug;21(5):849-56
references.pmid: 9267534
references.citation: Mol Psychiatry. 2003 Aug;8(8):721-37, 715
references.pmid: 12888801
references.citation: Neurotoxicology. 2001 Oct;22(5):593-9
references.pmid: 11770880
references.citation: Alcohol Alcohol. 1998 May-Jun;33(3):195-201
references.pmid: 9632044
references.citation: Alcohol. 2010 Feb;44(1):27-37
references.pmid: 20113872
references.citation: Int J Dev Neurosci. 2009 May;27(3):249-56
references.pmid: 19437591
references.citation: Int J Neurosci. 1997 Jan;89(1-2):119-32
references.pmid: 9134450
references.citation: PLoS Med. 2006 Apr;3(4):e101
references.pmid: 16478293
references.citation: Alcohol Alcohol. 2006 Mar-Apr;41(2):126-32
references.pmid: 16314425
references.citation: Science. 2000 Feb 11;287(5455):1056-60
references.pmid: 10669420
references.citation: Neurobiol Aging. 2011 Aug;32(8):1452-65
references.pmid: 19833411
references.citation: Epilepsia. 2010 Jul;51 Suppl 3:106-9
references.pmid: 20618413
references.citation: Alcohol Clin Exp Res. 1997 Sep;21(6):1010-7
references.pmid: 9309310
references.citation: Alcohol. 1993 Mar-Apr;10(2):169-78
references.pmid: 8442896
references.citation: Mol Pharmacol. 2011 Sep;80(3):446-57
references.pmid: 21697273
references.citation: Nature. 2011 Jul 27;477(7363):171-8
references.pmid: 21796121
references.citation: Brain Res Dev Brain Res. 2001 May 31;128(1):63-72
references.pmid: 11356263
references.citation: J Neurophysiol. 2005 Mar;93(3):1317-25
references.pmid: 15483067
references.citation: Neurotoxicol Teratol. 2012 Jan-Feb;34(1):128-35
references.pmid: 21871563
references.citation: Neurotoxicol Teratol. 1995 Jul-Aug;17(4):445-62
references.pmid: 7565491
references.citation: J Neurotrauma. 1995 Oct;12(5):883-90
references.pmid: 8594215
references.citation: Schizophr Bull. 2012 Sep;38(5):950-7
references.pmid: 22355184
references.citation: Ment Retard Dev Disabil Res Rev. 2001;7(4):267-75
references.pmid: 11754521
references.citation: Neuroscience. 2001;102(3):527-40
references.pmid: 11226691
references.citation: Cogn Behav Pract. 2010 May 1;17(2):203-212
references.pmid: 20473352
references.citation: Behav Neurosci. 2007 Dec;121(6):1306-15
references.pmid: 18085883
references.citation: Int J Dev Neurosci. 2011 Nov;29(7):733-42
references.pmid: 21664448
references.citation: Neuroscience. 2010 Oct 13;170(2):645-54
references.pmid: 20603193
references.citation: Curr Opin Neurobiol. 2012 Jun;22(3):537-44
references.pmid: 22079494
references.citation: J Neurodev Disord. 2009 Jun;1(2):172-81
references.pmid: 20664807
references.citation: Trends Neurosci. 2012 Jan;35(1):57-67
references.pmid: 22154068
references.citation: Hippocampus. 1997;7(2):232-8
references.pmid: 9136052
references.citation: Cell Biochem Funct. 1991 Jul;9(3):215-22
references.pmid: 1661209
references.citation: J Dev Behav Pediatr. 2011 Jun;32(5):384-92
references.pmid: 21654404
references.citation: Ageing Res Rev. 2004 Nov;3(4):383-406
references.pmid: 15541708
references.citation: Trends Mol Med. 2011 Aug;17(8):452-62
references.pmid: 21514225
references.citation: Trends Neurosci. 2005 Jun;28(6):334-40
references.pmid: 15927690
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5359-64
references.pmid: 19273846
references.citation: Brain Dev. 1982;4(1):1-6
references.pmid: 7039389