Excitation-transcription coupling, neuronal gene expression and synaptic plasticity

Excitation-transcription coupling (E-TC) links synaptic and cellular activity to nuclear gene transcription. It is generally accepted that E-TC makes a crucial contribution to learning and memory through its role in underpinning long-lasting synaptic enhancement in late-phase long-term potentiation and has more recently been linked to late-phase long-term depression: both processes require de novo gene transcription, mRNA translation and protein synthesis. E-TC begins with the activation of glutamate-gated N-methyl-d-aspartate-type receptors and voltage-gated L-type Ca2+ channels at the membrane and culminates in the activation of transcription factors in the nucleus. These receptors and ion channels mediate E-TC through mechanisms that include long-range signalling from the synapse to the nucleus and local interactions within dendritic spines, among other possibilities. Growing experimental evidence links these E-TC mechanisms to late-phase long-term potentiation and learning and memory. These advances in our understanding of the molecular mechanisms of E-TC mean that future efforts can focus on understanding its mesoscale functions and how it regulates neuronal network activity and behaviour in physiological and pathological conditions. Synaptic or neuronal activity can trigger transcriptional changes in the nucleus that are important for learning and memory. Tsien, Ma and co-workers here provide a comprehensive review of the complex signalling pathways involved in this excitation-transcription coupling.

Automated summary

Excitation-transcription coupling (E-TC) plays a crucial role in linking synaptic and cellular activity to nuclear gene transcription, contributing to learning and memory. E-TC is mediated by long-range signaling from the synapse to the nucleus and local interactions within dendritic spines. Understanding the molecular mechanisms of E-TC can provide insights into its mesoscale functions and its regulation of neuronal network activity and behavior in physiological and pathological conditions.