Chemo-electrical Signaling, Protein Translocation, and Neuronal Transcription

In this chapter, we provide an in-depth review of the molecular mechanisms underlying excitation-transcription (E-T) coupling in neuronsNeurons, a process crucial for neuronal plasticity and brain function adaptation. We discuss the roles of chemical signaling, membrane potential, intracellular calcium, and signaling molecules in bridging the spatial divide between synaptic activity and the nuclear transcription machinery. We highlight key foundational studies on E-T coupling and recent advances in understanding the molecular basis of this process. We also delve into the roles of N-methyl-D-aspartate receptors (NMDARs) and L-type Ca2+ channel (LTCC) in synaptic plasticity, explore the localization of neuronal LTCC isoforms, and consider the potential of Ca2+/CaM as a translocating signaling protein. Furthermore, we review the evidence for the behavioral impact of E-T coupling and its implications for neuropsychiatric diseases. We conclude the chapter with discussion of open questions in the field, emphasizing that the development of new cell biology tools for in vitro and in vivo studies will greatly enhance our understanding of activity-dependent gene expression.