Fig. 1. Arc is the first inducible dendritic mRNA. A, B, Views of the rat hippocampal formation showing the distribution of Arc mRNA, using nonradioactive in situ hybridization with digoxygenin-labeled antisense riboprobe. C, Labeling of the rat hippocampal formation, using a digoxygenin-labeled sense probe for Arc mRNA. A, Basal expression ofArc mRNA in the dentate gyrus overall is low, but a small number of neurons that show a high level of expression appear as occasional clusters. Note that basal levels of Arc mRNA are lower in the dentate molecular layer than in the dendritic lamina of CA1. B, This pattern is altered dramatically by ECS when Arc mRNA is induced broadly in dentate granule cells and migrates throughout the dendritic layer. C, Hybridization using an Arc sense probe yielded only background labeling. CA1 and CA3represent the subfields of the hippocampus. DG, Dentate gyrus. Arrowheads indicate the hippocampal fissure, the distal limit of the dentate molecular layer. Scale bar, 250 μm.D–I, Bright-field views of the dorsal limb of the dentate gyrus comparing the localization of Arc mRNA with NGFI-A mRNA and COX-2 mRNA after induction by a single ECS, using digoxygenin-labeled antisense riboprobe. Expression of these mRNAs is low in nonstimulated rats (D, Arc; F, NGFI-A; H, COX-2), and all are elevated substantially by a single ECS (E, Arc;G, NGFI-A; I, COX-2). Note thatArc mRNA was present throughout the dentate molecular layer 1 hr after ECS, but NGFI-A and COX-2 mRNA were confined to the stratum granulosa (SG) despite strong induction. This suggests that the dendritic localization of Arc mRNA is not simply the result of random diffusion but, rather, is the product of selective transport. Arrowheads indicate the distal limit of granule cell dendrites. Scale bar, 100 μm.