Regulation of gene expression involved in conveying information between synapses and nuclei in neurons

Since G protein-coupled receptors (GPCRs) potentiate the activity of the N-methyl-D-aspartate receptor (NMDA-R), we comprehensively investigated gene expression induced by the stimulation of GPCRs in culture. Potentiation of NMDA-R mediated by the activation of PAC1, a GPCR, with PACAP immediately activated a limited number of genes upon Ca^<2+> signals. The mRNA expression of the brain-derived neurotrophic factor exon IV-IX (Bdnf-eIV) is totally controlled by Ca^<2+>/calcineurin, leading to the CRE/CREB-dependent transcription. Stimulation of NMDA-R under the activation of PAC1 synergistically increased Bdnf-eIV mRNA expression through the selective activation of calcineurin, leading to translocation of TORC1 to nucleus and activation of CREB-KID domain. The Ca^<2+>/calcineurin-dependent mRNA expression was also induced by direct stimulation of PKA or PKC pathway and, furthermore, by that of the dopamine D1 or β-adrenergic receptor. Thus, the potentiation of NMDA-R activity mediated by GPCR induces activity-dependent gene expression through calcineurin pathway, possibly regardless of the type of neurotransmission.