Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity

Nat Neurosci. 2001 Mar;4(3):261-7. doi: 10.1038/85109.


Information storage in the nervous system requires transcription triggered by synaptically evoked calcium signals. It has been suggested that translocation of calmodulin into the nucleus, initiated by submembranous calcium transients, relays synaptic signals to CREB. Here we show that in hippocampal neurons, signaling to CREB can be activated by nuclear calcium alone and does not require import of cytoplasmic proteins into the nucleus. The nucleus is particularly suited to integrate neuronal firing patterns, and specifies the transcriptional outputs through a burst frequency-to-nuclear calcium amplitude conversion. Calcium release from intracellular stores promotes calcium wave propagation into the nucleus, which is critical for CREB-mediated transcription by synaptic NMDA receptors. Pharmacological or genetic modulation of nuclear calcium may directly affect transcription-dependent memory and cognitive functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Calmodulin / metabolism
  • Calmodulin / pharmacology
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Rats, Long-Evans
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Wheat Germ Agglutinins / pharmacology


  • Calcium Channels, L-Type
  • Calmodulin
  • Cyclic AMP Response Element-Binding Protein
  • Wheat Germ Agglutinins