How the expression of immediate early genes (IEGs) is controlled in response to neurotransmissions is unknown. Using cultured rat cortical cells, we investigated the expression of IEGs regulated by Ca2+ and/or cAMP signals. The expression of c-fos was transiently induced by treatment of cells with high potassium (high K+), which evoked depolarization, or forskolin, an adenylate cyclase activator. c-fos expression was persistently and synergistically induced by simultaneous treatment with high K+ and forskolin via cAMP-response element (CRE). Microarray analysis indicated the expression profiles of IEGs caused by depolarization in the presence or absence of forskolin. When a novel index was included to investigate the profile of IEGs, we found that high K+-induced expression of IEGs was stimulatory or negatively changed in the presence of forskolin, suggesting distinct convergent effects of Ca2+ and CAMP signals on the expression of IEGs. (C) 2015 Elsevier Inc. All rights reserved.