Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression

Neuropsychopharmacology. 2015 Jan;40(2):480-7. doi: 10.1038/npp.2014.197. Epub 2014 Aug 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fear / drug effects
  • Fear / physiology*
  • GABA-A Receptor Agonists / pharmacology
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / physiology*
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Muscimol / pharmacology
  • Rats, Sprague-Dawley
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, Kainic Acid / metabolism
  • Time Factors

Substances

  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Agonists
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Muscimol
  • 6-Cyano-7-nitroquinoxaline-2,3-dione