title: The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is required for reconsolidation of a Pavlovian fear memory.
abstract: The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is an immediate-early gene that has been widely implicated in synaptic plasticity and in the consolidation of a variety of hippocampal- and amygdala-dependent memory tasks. The functional role of Arc/Arg3.1 in memory reconsolidation processes, however, has not been systematically studied. In the present study, we examined the role of Arc/Arg3.1 in the reconsolidation of an amygdala-dependent auditory pavlovian fear memory. We show that Arc/Arg3.1 protein is regulated in the lateral nucleus of the amygdala (LA) by retrieval of an auditory fear memory. Next, we show that antisense knockdown of Arc/Arg3.1 in the LA impairs fear memory reconsolidation of both a recent (1-d-old) as well as a well-consolidated (2-week-old) fear memory; that is, post-retrieval short-term memory, tested at 3 h after retrieval, is intact, whereas post-retrieval long-term memory, tested approximately 24 h after retrieval, is significantly impaired. The effect of Arc/Arg3.1 knockdown was observed to be time limited and specific to an actively reactivated fear memory. Moreover, the reconsolidation deficit induced by Arc/Arg3.1 knockdown was not found to be sensitive to spontaneous recovery, reinstatement, or a shift in the testing context, suggesting that our behavioral effects are not attributable to facilitated extinction. Collectively, our findings provide the first comprehensive look at the functional role of Arc/Arg3.1 in memory reconsolidation processes in the mammalian brain.
authors.affiliation: Department of Psychology and Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Maddox
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Schafe
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003214:Conditioning, Classical / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein