Analyses of fear memory in Arc/Arg3.1-deficient mice: intact short-term memory and impaired long-term and remote memory

Kazuyuki Yamada, Chihiro Homma, Kentaro Tanemura, Toshio Ikeda, Shigeyoshi Itohara, Yoshiko Nagaoka

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DOI: 10.4236/wjns.2011.11001                

Abstract

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) was originally identified in patients with seizures. It is densely distributed in the hip-pocampus and amygdala in particular. Because the expression of Arc/Arg3.1 is regulated by nerve in-puts, it is thought to be an immediate early gene. As shown both in vitro and in vivo, Arc/Arg3.1 is in-volved in synaptic consolidation and regulates some forms of learning and memory in rats and mice [1,2]. Furthermore, a recent study suggests that Arc/Arg3.1 may play a significant role in signal transmission via AMPA-type glutamate receptors [3-5]. Therefore, we conducted a detailed analysis of fear memory in Arc/Arg3.1-deficient mice. As previously reported, the knockout animals exhib-ited impaired fear memory in both contextual and cued test situations. Although Arc/Arg3.1-deficient mice showed almost the same performance as wild-type littermates 4 hr after a conditioning trial, their performance was impaired in the retention test after 24 hr or longer, either with or without reconsolidation. Immunohistochemical analyses showed an abnormal density of GluR1 in the hip-pocampus of Arc/Arg3.1-deficient mice; however, an application of AMPA potentiator did not improve memory performance in the mutant mice. Memory impairment in Arc/Arg3.1-deficient mice is so ro-bust that the mice provide a useful tool for devel-oping treatments for memory impairment.

Keywords

Activity-Regulated Cytoskeleton-Associated Protein (Arc/Arg3.1); Knockout (Ko) Mouse; Short- Term Memory; Long-Term Memory; Reconsolidation; Ampa Receptor

Conflicts of Interest

The authors declare no conflicts of interest.

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