The article discusses the role of calcium in regulating neuronal gene expression, particularly focusing on the induction of the gene encoding brain-derived neurotrophic factor (BDNF). Calcium influx into neurons, often initiated by membrane depolarization, triggers a series of signaling events that lead to the activation of transcription factors and the induction of new gene expression. The authors identify three key points in this process where the specificity of gene induction can be regulated: the route of calcium entry, the phosphorylation of the transcription factor CREB, and the recruitment of active transcription factors to the BDNF promoter. They find that the ability of calcium to induce BDNF transcription is influenced by the type of calcium channel through which it enters the cell, the phosphorylation state of CREB, and the presence of specific transcription factors. These findings refine the understanding of how different types of neuronal stimuli can activate distinct transcriptional responses, contributing to long-term changes in neuronal structure and function. The article also explores the role of NMDA receptors and voltage-gated calcium channels in calcium signaling and their specific contributions to gene expression. Finally, it highlights the importance of CREB in mediating the effects of calcium on gene transcription and the potential mechanisms by which calcium-specific phosphorylation of CREB may regulate its interaction with other transcription factors.The article discusses the role of calcium in regulating neuronal gene expression, particularly focusing on the induction of the gene encoding brain-derived neurotrophic factor (BDNF). Calcium influx into neurons, often initiated by membrane depolarization, triggers a series of signaling events that lead to the activation of transcription factors and the induction of new gene expression. The authors identify three key points in this process where the specificity of gene induction can be regulated: the route of calcium entry, the phosphorylation of the transcription factor CREB, and the recruitment of active transcription factors to the BDNF promoter. They find that the ability of calcium to induce BDNF transcription is influenced by the type of calcium channel through which it enters the cell, the phosphorylation state of CREB, and the presence of specific transcription factors. These findings refine the understanding of how different types of neuronal stimuli can activate distinct transcriptional responses, contributing to long-term changes in neuronal structure and function. The article also explores the role of NMDA receptors and voltage-gated calcium channels in calcium signaling and their specific contributions to gene expression. Finally, it highlights the importance of CREB in mediating the effects of calcium on gene transcription and the potential mechanisms by which calcium-specific phosphorylation of CREB may regulate its interaction with other transcription factors.