Learning-induced arg 3.1/arc mRNA expression in the mouse brain.

The effector immediate-early gene (IEG) arg 3.1, also called arc, encodes a protein interacting with the neuronal cytoskeleton. The selective localization of arg 3.1/arc mRNA in activated dendritic segments suggests that the arg 3.1/arc protein may be synthesized at activated post-synaptic sites and that arg 3.1/arc could participate in structural and functional modifications underlying cognitive processes like memory formation. To analyze whether learning itself is sufficient to trigger expression of arg 3.1/arc, we developed a one-trial learning paradigm in which mice learned to enter a dark compartment to escape from an aversively illuminated area. Arg 3.1/arc mRNA expression was analyzed by in situ hybridization in three groups of mice as follows: a control group with no access to the dark compartment, a learning group having access to the dark compartment for one trial, and a retrieval group having access to the dark compartment for two trials on consecutive days. All animals from the learning and retrieval groups escaped the illuminated area, and those tested 24 h later (retrieval group) showed a strongly reduced latency to enter the dark compartment, demonstrating the validity of our learning paradigm to induce long-term memory. Our results show that acquisition of a simple task results in a brain area-specific biphasic increase in arg 3.1/arc mRNA expression 15 min and 4.5 h post-training. This increase was detected specifically in the learning group but neither in the control nor in the retrieval groups. The pattern of arg 3.1/arc mRNA expression corresponds temporally to the two mRNA- and protein-synthesis-dependent periods of long-term memory formation. Our study provides the first unequivocal evidence that arg 3.1/arc expression is induced by a learning task and strongly suggests a role of arg 3.1/arc mRNA in the early and late cellular mechanisms underlying the stabilization of the memory trace.