Neuronal activity-dependent gene regulation in the developing neocortex

The basic neuronal circuits are formed through inherent developmental programs, but these initial circuits are known to be modified by neuronal electrical activity. Our previous works have demonstrated the influence of neuronal activity on branch formation of developing thalamocortical and cortical axons, and have uncovered the effector molecules that govern activity-dependent axon branching. The intriguing question that follows is the mechanism by which neuronal activity is transduced into molecular signals in neocortical neurons. While biochemical and molecular biological studies have revealed the basic molecular mechanisms, including transcription factors, it is unknown which physiological stimulation efficiently affects gene expression in cortical neurons. Furthermore, it is still unclear how neuronal activity enhances the expression of a subset of genes spatiotemporally in the nucleus. To gain insights into these issues, we conducted live imaging of the promoter activity of BDNF, an activity-dependent gene, and single-molecule imaging of transcription and epigenetic factors, such as CREB and CBP. Here I will demonstrate the results and discuss the gene regulatory mechanisms for activity-dependent circuit formation.