Experience-Dependent Regulation of the Immediate-Early Gene Arc Differs across Brain Regions

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Abstract
Previously, we demonstrated that initial acquisition of a lever-press task resulted in higher levels of activity-regulated cytoskeleton-associated protein (Arc) mRNA induction than did overtrained performance (Kelly and Deadwyler, 2002). The present study extends this finding by characterizing (1) the behavioral regulation of Arc protein expression, (2) the time course of decay of Arc mRNA signal in different brain regions immediately after the initial acquisition session, and (3) the persistence of Arc mRNA induction in those same brain regions across sessions. Rats killed after initial acquisition of a simple lever-press response demonstrated significantly elevated levels of Arc protein. Interestingly, of the brain regions that demonstrated Arc mRNA induction 30 min after the acquisition session, there was a differential rate in signal decay, with only half of the regions continuing to demonstrate elevated levels of Arc at 60 min. Similarly, the extent to which Arc mRNA induction persisted across days also varied across brain regions. An unexpected outcome was that areas such as CA1 and CA3 that showed the least persistence in Arc activation immediately after the initial acquisition session showed the greatest perseverance of induction across days of training. Finally, animals less proficient at the task expressed higher levels of Arc mRNA than animals that acquired the task more quickly. Taken together, the results show that Arc mRNA and protein were regulated in an experience-dependent manner; however, the fact that the time course of Arc mRNA expression differed across brain structures suggests a differential rate of consolidation of the newly acquired behavior across specific brain regions.