NMDA-mediated and self-induced bdnf exon IV transcriptions are differentially regulated in cultured cortical neurons

Activity-dependent transcriptional up-regulation of bdnf (brain-derived neurotrophic factor) is involved in regulating many aspects of neuronal functions. The NMDA (N-methyl-d-aspartic acid)-mediated and BDNF-mediated exon IV transcription may represent mechanistically different responses, and relevant to activity-dependent changes in neurons. We found that the activities of ERK (extracellular signal-regulated kinase), CaM KII/IV (calmodulin-dependent protein kinase II and IV), PI3K (phosphoinositide 3-kinase), and PLC (phospholipase C) are required for NMDA receptor-mediated bdnf exon IV transcription in cultured cortical neurons. In contrast, the BDNF-induced and TrkB-dependent exon IV transcription was regulated by ERK and CaM KII/IV, but not by PI3K and PLC. While ERK and CaM KII/IV are separate signaling pathways in BDNF-stimulated neurons, CaM KII/IV appeared to regulate exon IV transcription through ERK in NMDA-stimulated neurons. Similarly, the PI3K and PLC signaling pathways converged on ERK in NMDA- but not BDNF-stimulated neurons. Our results implicate that the NMDA-induced and the self-maintenance of bdnf transcription are differentially regulated.