Reconsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens

Hippocampus. 2017 May;27(5):596-607. doi: 10.1002/hipo.22715. Epub 2017 Mar 7.


Systems consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.

Keywords: anterior cingulate cortex; nucleus reuniens; reconsolidation; remote memory; systems consolidation.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology
  • Calcium Channel Blockers / pharmacology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Fear / drug effects
  • Fear / physiology*
  • GABA-A Receptor Agonists / pharmacology
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / physiology*
  • Lidocaine / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology*
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Midline Thalamic Nuclei / physiology*
  • Muscimol / pharmacology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Nimodipine / pharmacology
  • Rats, Wistar
  • Voltage-Gated Sodium Channel Blockers / pharmacology


  • Calcium Channel Blockers
  • GABA-A Receptor Agonists
  • Voltage-Gated Sodium Channel Blockers
  • Muscimol
  • Nimodipine
  • Lidocaine