Upregulation of the immediate early gene arc in the brains of rats exposedto environmental enrichment: implications for molecular plasticity

Exposure to an enriched environment, a procedure that induces plasticity in the cerebral cortex, is associated with pronounced morphological changes, including higher density of dendritic spines, enlargement of synaptic bouto ns, and other putative correlates of altered neurotransmission. Recently, i t has been demonstrated that animals reared in an enriched environment sett ing for 3 weeks have less neuronal damage as a result of seizures and have decreased rates of spontaneous apoptosis. Even though clear morphological m odifications are observed in the cerebral cortex of animals exposed to heig htened environmental complexity, the: molecular mechanisms that underlie su ch modifications are yet to be described. In the present work, we investiga ted the expression of the immediate early gene are in the cortex of animals exposed to an enriched environment. Animals were exposed daily, for 1 h, t o an enriched environment, for a total period of 3 weeks. Brains were proce ssed for in-situ hybridization against arc mRNA. We found a marked upregula tion of are mRNA in the cerebral cortex of animals exposed to the enriched environment, when compared to undisturbed controls, an effect that was most pronounced in cortical layers III and V. Animals in an additional control group that were handled for 5 min daily, displayed intermediate levels of a re mRNA. Furthermore, are expression was upregulated in the CA1, CA2 and CA 3 hippocampal subfields and in the striatum, but to a lesser extent in the dentate gyrus of animals exposed to an enriched environment, as compared to the two control groups. Our results support the association between the up regulation of the immediate early gene are and plasticity-associated anatom ical changes in the cerebral cortex of the adult mammal. (C) 2001 Elsevier Science B.V. All rights reserved.