Somatic action potentials are sufficient for late-phase LTP-related cell signaling

Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3962-7. doi: 10.1073/pnas.062510599. Epub 2002 Mar 12.


A question of critical importance confronting neuroscientists today is how biochemical signals initiated at a synapse are conveyed to the nucleus. This problem is particularly relevant to the generation of the late phases of long-term potentiation (LTP). Here we provide evidence that some signaling pathways previously associated with late-LTP can be activated in hippocampal CA1 neurons without synaptic activity; somatic action potentials, induced by backfiring the cells, were found to be sufficient for phosphorylation of extracellular signal-regulated kinase-1/2 and cAMP response element-binding protein, as well as for induction of zif268. Furthermore, such antidromic stimulation was adequate to rescue "tagged" synapses (early-LTP) from decay. These results show that a synapse-to-nucleus signal is not necessary for late-phase LTP-associated signaling cascades in the regulation of gene expression.

MeSH terms

  • Action Potentials* / drug effects
  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA-Binding Proteins / metabolism
  • Early Growth Response Protein 1
  • Gene Expression Regulation / drug effects
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Immediate-Early Proteins*
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Long-Term Potentiation* / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nifedipine / pharmacology
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Synapses / drug effects
  • Synapses / metabolism
  • Transcription Factors / metabolism


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • Transcription Factors
  • Mitogen-Activated Protein Kinases
  • Kynurenic Acid
  • Nifedipine