Excitation-transcription coupling, neuronal gene expression and synaptic plasticity

Nat Rev Neurosci. 2023 Nov;24(11):672-692. doi: 10.1038/s41583-023-00742-5. Epub 2023 Sep 29.

Abstract

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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression
  • Hippocampus / physiology
  • Humans
  • Long-Term Potentiation / physiology
  • Neuronal Plasticity* / physiology
  • Neurons / metabolism
  • Receptors, N-Methyl-D-Aspartate* / metabolism
  • Synapses / metabolism

Substances

  • Receptors, N-Methyl-D-Aspartate