title: Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression.
abstract: After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory.
authors.affiliation: Department of Psychology, McGill University, Montreal, QC, Canada.
authors.forename: Einar Ö
authors.initials: EÖ
authors.lastname: Einarsson
authors.affiliation: Department of Psychology, McGill University, Montreal, QC, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pors
authors.affiliation: Department of Psychology, McGill University, Montreal, QC, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Nader
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors
references.citation: Nature. 2011 May 26;473(7348):514-8
references.pmid: 21532590
references.citation: Trends Cogn Sci. 2013 Mar;17(3):111-20
references.pmid: 23369831
references.citation: Learn Mem. 2005 Sep-Oct;12(5):445-6
references.pmid: 16166399
references.citation: Science. 2004 May 7;304(5672):881-3
references.pmid: 15131309
references.citation: Science. 2013 Mar 15;339(6125):1290-5
references.pmid: 23493706
references.citation: J Neurosci. 1999 Dec 15;19(24):RC45
references.pmid: 10594089
references.citation: Nat Rev Neurosci. 2005 Feb;6(2):119-30
references.pmid: 15685217
references.citation: Curr Biol. 2010 Aug 10;20(15):1336-44
references.pmid: 20637623
references.citation: Nat Commun. 2011 Oct 18;2:504
references.pmid: 22009036
references.citation: Psychol Rev. 1995 Jul;102(3):419-457
references.pmid: 7624455
references.citation: Learn Mem. 2012 Jul 16;19(8):315-8
references.pmid: 22802592
references.citation: Curr Opin Neurobiol. 1995 Apr;5(2):169-77
references.pmid: 7620304
references.citation: Science. 2009 May 15;324(5929):951-5
references.pmid: 19342552
references.citation: Learn Mem. 2007 Mar 08;14(3):200-3
references.pmid: 17351145
references.citation: Cell. 2011 Oct 28;147(3):678-89
references.pmid: 22019004
references.citation: Neuron. 2002 Oct 24;36(3):527-38
references.pmid: 12408854
references.citation: Neurobiol Aging. 1999 Jul-Aug;20(4):363-72
references.pmid: 10604429
references.citation: Learn Mem. 2007 Apr 10;14(4):313-7
references.pmid: 17522020
references.citation: Cell. 2009 Nov 13;139(4):814-27
references.pmid: 19914173
references.citation: Nat Neurosci. 2007 May;10(5):555-7
references.pmid: 17396121
references.citation: Neuropsychologia. 2010 Jul;48(8):2339-56
references.pmid: 20430044
references.citation: Nature. 2000 Aug 17;406(6797):722-6
references.pmid: 10963596
references.citation: Psychol Bull. 1992 Nov;112(3):433-45
references.pmid: 1438637
references.citation: Hippocampus. 2012 May;22(5):1092-5
references.pmid: 22120981
references.citation: Learn Mem. 2012 Sep 14;19(10):449-52
references.pmid: 22984282
references.citation: J Neurosci. 2005 Sep 28;25(39):8978-87
references.pmid: 16192388
references.citation: Learn Mem. 2009 Oct 29;16(11):722-9
references.pmid: 19875506
references.citation: Science. 1988 Aug 5;241(4866):701-3
references.pmid: 2899909
references.citation: Science. 2007 Apr 6;316(5821):76-82
references.pmid: 17412951
references.citation: J Neurosci. 1999 Feb 1;19(3):1106-14
references.pmid: 9920672
references.citation: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8456-60
references.pmid: 21531906
references.citation: Annu Rev Psychol. 2010;61:141-67
references.pmid: 19575608
references.citation: Curr Opin Neurobiol. 1997 Apr;7(2):217-27
references.pmid: 9142752