title: Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure.
abstract: Abnormal cortical circuitry and function as well as distortions in the modulatory neurological processes controlling cortical plasticity have been argued to underlie the origin of autism. Here, we chemically distorted those processes using an antidepressant drug-exposure model to generate developmental neurological distortions like those characteristics expressed in autism, and then intensively trained altered young rodents to evaluate the potential for neuroplasticity-driven renormalization. We found that young rats that were injected s.c. with the antidepressant citalopram from postnatal d 1-10 displayed impaired neuronal repetition-rate following capacity in the primary auditory cortex (A1). With a focus on recovering grossly degraded auditory system processing in this model, we showed that targeted temporal processing deficits induced by early-life antidepressant exposure within the A1 were almost completely reversed through implementation of a simple behavioral training strategy (i.e., a modified go/no-go repetition-rate discrimination task). Degraded parvalbumin inhibitory GABAergic neurons and the fast inhibitory actions that they control were also renormalized by training. Importantly, antidepressant-induced degradation of serotonergic and dopaminergic neuromodulatory systems regulating cortical neuroplasticity was sharply reversed. These findings bear important implications for neuroplasticity-based therapeutics in autistic patients.
authors: Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China; NYU-ECNU Institute of Brain and Cognitive Science, NYU Shanghai, Shanghai 200062, China; xmzhou@bio.ecnu.edu.cn michael.merzenich@positscience.com.
authors: Xiaoming
authors: X
authors: Zhou
authors: Departments of Neurobiology and Anatomical Sciences.
authors: Jordan Y-F
authors: JY
authors: Lu
authors: Departments of Neurobiology and Anatomical Sciences.
authors: Ryan D
authors: RD
authors: Darling
authors: Departments of Neurobiology and Anatomical Sciences, Psychiatry and Human Behavior, and.
authors: Kimberly L
authors: KL
authors: Simpson
authors: Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China;
authors: Xiaoqing
authors: X
authors: Zhu
authors: Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China;
authors: Fang
authors: F
authors: Wang
authors: Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China;
authors: Liping
authors: L
authors: Yu
authors: Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China;
authors: Xinde
authors: X
authors: Sun
authors: Keck Center for Integrative Neuroscience, University of California, San Francisco, CA 94143 xmzhou@bio.ecnu.edu.cn michael.merzenich@positscience.com.
authors: Michael M
authors: MM
authors: Merzenich
authors: Departments of Neurobiology and Anatomical Sciences, Psychiatry and Human Behavior, and Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216; and.
authors: Rick C S
authors: RC
authors: Lin
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000503:physiopathology*; D005260:Female; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017367:Selective Serotonin Reuptake Inhibitors
keywords: antidepressant exposure; autism; behavioral training; cortical network; recovery of function
references: Neuropsychopharmacology. 2006 Jan;31(1):47-57
references: 16012532
references: J Neurosci. 2006 Jun 28;26(26):6897-906
references: 16807320
references: Pediatrics. 2005 Feb;115(2):411-25
references: 15687451
references: Nat Neurosci. 2000 Sep;3(9):904-10
references: 10966621
references: J Child Psychol Psychiatry. 2013 Feb;54(2):195-205
references: 23320807
references: J Psychiatry Neurosci. 2003 Jul;28(4):247-50
references: 12921219
references: J Neurosci. 1998 Sep 1;18(17):6914-27
references: 9712661
references: Nat Commun. 2012;3:843
references: 22588305
references: Pediatrics. 2014 May;133(5):e1241-8
references: 24733881
references: Int Rev Neurobiol. 2005;71:1-26
references: 16512344
references: Science. 2012 Sep 14;337(6100):1301-3
references: 22984058
references: Neuroreport. 2005 Mar 15;16(4):329-32
references: 15729132
references: J Neurosci. 2011 Nov 16;31(46):16709-15
references: 22090498
references: Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18465-70
references: 22025710
references: Biol Psychiatry. 2007 Nov 1;62(9):1015-21
references: 17572391
references: Nat Neurosci. 2008 Aug;11(8):957-65
references: 18604205
references: Pediatrics. 2010 Jan;125(1):e17-23
references: 19948568
references: Front Cell Neurosci. 2013 May 10;7:67
references: 23675318
references: Genes Brain Behav. 2003 Oct;2(5):255-67
references: 14606691
references: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13900-5
references: 20643928
references: Nat Neurosci. 2009 Jan;12(1):26-8
references: 19079250
references: J Neurosci. 2013 Aug 21;33(34):13713-23
references: 23966693
references: Trends Pharmacol Sci. 2010 Feb;31(2):60-5
references: 19963284
references: Neuron. 2005 Apr 7;46(1):65-74
references: 15820694
references: Neuron. 2011 Jun 9;70(5):806-8
references: 21658575
references: J Neurosci. 2003 Nov 26;23(34):10765-75
references: 14645468
references: Nature. 2013 Jan 17;493(7432):371-7
references: 23172145
references: Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2:17221-7
references: 23045665
references: J Spec Pediatr Nurs. 2009 Jul;14(3):183-91
references: 19614827
references: Neuron. 2011 Jun 23;70(6):1218-25
references: 21689606
references: Neuropsychologia. 2011 Apr;49(5):1378-82
references: 21333661
references: Anat Rec (Hoboken). 2011 Oct;294(10):1646-52
references: 21901839
references: Curr Opin Neurobiol. 2007 Feb;17(1):103-11
references: 17275283
references: J Comp Neurol. 2000 Jun 19;422(1):140-57
references: 10842223
references: Brain Res. 2002 Jun 28;942(1-2):109-19
references: 12031859
references: Biol Psychiatry. 2007 Feb 15;61(4):521-37
references: 17276749
references: J Neurosci. 2010 Nov 3;30(44):14595-609
references: 21048117
references: J Child Psychol Psychiatry. 2005 Dec;46(12):1255-68
references: 16313426
references: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15935-40
references: 17895375
references: Arch Gen Psychiatry. 2009 Jun;66(6):583-90
references: 19487623
references: Nature. 2008 Aug 14;454(7206):838-9
references: 18704077
references: J Chem Neuroanat. 2011 Jul;41(4):281-93
references: 21640185
references: Pediatrics. 2012 May;129(5):e1301-10
references: 22529279
references: Int J Dev Neurosci. 2005 Apr-May;23(2-3):189-99
references: 15749245
references: Neuropharmacology. 2008 Nov;55(6):994-1005
references: 18789954
references: Res Dev Disabil. 2010 May-Jun;31(3):790-9
references: 20207104
references: Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3107-12
references: 23319621
references: Brain Res Brain Res Rev. 2003 Apr;42(1):33-84
references: 12668290