FBS Colloquia No.169Cellular and Molecular Neurobiology Group

Neuronal activity-dependent dynamics of gene expression in cortical neurons revealed by single-molecule imaging

Transcriptional regulation is involved in neuronal activity-dependent processes that control neuronal circuit formation and synaptic plasticity. An intriguing question is how neuronal activity influences transcriptional processes such as binding and dissociation of transcription factors to their target DNA sites or interactions between transcription factors and their cofactors. Here, we investigated activity-dependence of DNA binding and dissociation events of cAMP-response element binding protein (CREB), a principal factor in activity-dependent transcription, in the nuclei of living cortical neurons using fine-tuned single-molecule imaging and optogenetic methods. We found that a significant fraction of CREB transiently resided in the restricted locations for several seconds, but not mutant CREB which cannot bind to the target sequence CRE (cAMP-response element). Furthermore, increased neuronal activity did not affect the CREB binding property, but markedly increased the number of restricted locations (hot spots) where CREB spots frequently resided. These results suggest that neuronal activity promotes CREB-dependent transcription by increasing the frequency of CREB binding to CRE sites.