SEQUENCE-SPECIFIC IMPAIRMENT OF LEARNING BY C-JUN ANTISENSE OLIGONUCLEOTIDES

HYBRIDIZATION studies revealed a differential accumulation of c-jun an d jun B mRNA in the hippocampus and cerebral cortex of rats trained on a foot-shock-motivated brightness discrimination. Supposing that earl y gene expression is functionally significant for plastic changes in t he brain, we used antisense phosphorothioate oligodeoxynucleotides (S- ODN) in vivo to study effects of specific inhibition of c-jun and jun B gene expression on learning and memory formation in rat brain. Discr imination performance of rats was impaired after intrahippocampal inje ction of anti-c-jun S-ODN but nor of anti-jun BS-ODN. These results im ply that topically injected antisense oligonucleotides affect process involved in learning and memory in a sequence-specific manner.