Identification and characterization of novel activity-dependent transcription factors in rat cortical neurons.

Using gene chip analyses, we have identified novel neuronal activity-dependent genes. Application of 25 mM KCl to mature (14-day culture) rat cortical neurons resulted in more than 1.5-fold induction of 19 genes and reduction of 42 genes among 1200 neural genes. Changes in the overall gene expression profiles appeared to be related to the reduction of excitability and induction of cellular survival signals. Among the genes identified, three transcriptional modulators [encoding Cbp/p300-interacting transactivator with ED-rich tail 2 (CITED2), CCAAT/enhancer binding protein beta (C/EBPbeta) and neuronal orphan receptor-1, (NOR1)] were newly identified as activity-dependent transcription factors, and two of these (CITED2 and NOR1) were found to be influenced by electroconvulsive shock (ECS). NOR1 was induced in specific brain regions by behavioral activation, such as exposure to a novel environment. Because the brain regions that exhibited the induction of these newly identified neuronal activity-dependent transcriptional modulators were distinct from those showing the induction of previously identified activity-dependent genes such as c-fos, these genes might be useful markers for mapping neuronal activity in vivo.