Selective zif268 mRNA induction in the perirhinal cortex of macaque monkeys during formation of visual pair-association memory

To elucidate the molecular basis of cognitive memory formation in the primate, transcriptional activation during learning of a visual pair-association (PA) task was evaluated systematically along the occipito-temporo-hippocampal pathway in the macaque monkey brain. Split-brain monkeys were used for intra-animal comparison, which enables elimination of animal-to-animal variation in gene expression. We found that the expression of the mRNA of an immediate-early gene (IEG), zif268, was up-regulated selectively in the perirhinal cortex (area 36) during the formation of PA memory compared to that during learning of a visual control task. The mRNA expression levels of another IEG, c-jun, were not up-regulated during the PA learning in any cortical areas examined. We also showed that cells strongly expressing zif268 mRNA accumulated in patches in area 36 during learning of the PA task. As the zif268 gene encodes a transcription factor, these results suggest that the activation of zif268 mRNA in area 36 may function as a trigger of the cascade of gene activation that leads to cellular events underlying neuronal reorganization for visual long-term memory formation.