Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning

Neurobiol Learn Mem. 2013 Nov;106:48-55. doi: 10.1016/j.nlm.2013.06.021. Epub 2013 Jul 16.


Mounting evidence suggests that long-lasting, protein synthesis-dependent changes in synaptic strength accompany both the initial acquisition and subsequent recall of specific memories. Within brain areas thought to be important for learning and memory, including the hippocampus, learning-related plasticity is likely mediated in part by NMDA receptor activation and experience-dependent changes in gene expression. In the present study, we examined the role of activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition, recall, and reconsolidation of memory in a trace fear conditioning paradigm. First, we show that the expression of Arc protein in ventral hippocampus (VH) is dramatically enhanced by memory recall 24h after the acquisition of trace fear conditioning, and that both memory recall and the associated recall-induced enhancement of Arc expression are blocked by pre-training administration of 2-amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect on memory recall, it significantly reduced both Arc protein expression and freezing behavior during subsequent testing sessions. Collectively, these results suggest that Arc/Arg3.1 protein plays an important functional role in both the initial acquisition of hippocampal-dependent memory and the reconsolidation of these memories after recall.

Keywords: Activity-regulated cytoskeletal protein; Gene expression; Hippocampus; Immediate-early gene; Memory reconsolidation; Rat.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Fear / physiology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • activity regulated cytoskeletal-associated protein
  • 2-Amino-5-phosphonovalerate