Sequence-specific impairment of learning by c-jun antisense oligonucleotides

Hybridization studies revealed a differential accumulation of c-jun and jun B mRNA in the hippocampus and cerebral cortex of rats trained on a foot-shock-motivated brightness discrimination. Supposing that early gene expression is functionally significant for plastic changes in the brain, we used antisense phosphorothioate oligo- deoxynucleotides (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. Discrimination performance of rats was impaired after intrahippo- campal injection of anti-c-jun S-ODN but not of anti-jun B S-ODN. These results imply that topically injected anti- sense oligonucleotides affect processes involved in learning and memory in a sequence-specific manner.