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

• Animals were trained in hippocampal-dependent trace fear conditioning.
• Arc expression was quantified in the ventral hippocampus after testing 24 h later.
• Memory recall enhances Arc expression and is blocked by pre-training administration of APV.
• Administration of Arc antisense ODNs prior to testing does not impair expression of trace fear conditioning.
• Administration of Arc antisense ODNs prior to testing blocks recall-induced Arc expression and memory reconsolidation.

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 24 h 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.