Suppression of c-fos induction in rat brain impairs retention of a brightness discrimination reaction.

Recently, the induction of transcription factor-encoding immediate-early genes such as c-fos was observed in distinct brain regions of rats trained to acquire a footshock-motivated brightness discrimination in a Y-maze. The functional relevance of inducible transcription factors for learning and memory formation is, however, not clear. To address this question in the present study, we have used a synthetic antisense phosphorothioate oligodeoxynucleotide to suppress in vivo the expression of c-fos in rat brain. Intrahippocampal application of the oligodeoxynucleotide 10 hr and 2 hr before starting a brightness discrimination training drastically reduced the induction of c-Fos immunoreactivity normally observed in limbic and cortical areas after the training session. Acquisition of the discrimination reaction was not affected by this treatment. In a relearning test 24 hr after the first training, retention of the discrimination reaction was specifically impaired compared with rats pretreated with control oligodeoxynucleotide or saline. Our findings are consistent with the hypothesis that the inducible transcription factor c-Fos is involved in processes underlying the formation of long-term memory.