Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus

Neuron. 1996 May;16(5):973-82. doi: 10.1016/s0896-6273(00)80120-8.


Gene expression regulated by the cAMP response element (CRE) has been implicated in synaptic plasticity and long-term memory. It has been proposed that CRE-mediated gene expression is stimulated by signals that induce long-term potentiation (LTP). To test this hypothesis, we made mice transgenic for a CRE-regulated reporter construct. We focused on long-lasting long-term potentiation (L-LTP), because it depends on cAMP-dependent protein kinase activity (PKA) and de novo gene expression. CRE-mediated gene expression was markedly increased after L-LTP, but not after decremental UP (D-LTP). Furthermore, inhibitors of PKA blocked L-LTP and associated increases in CRE-mediated gene expression. These data demonstrate that the signaling required for the generation of L-LTP but not D-LTP is sufficient to stimulate CRE-mediated transcription in the hippocampus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / physiology
  • Cyclic AMP / physiology
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Gene Expression Regulation
  • Hippocampus / physiology*
  • Long-Term Potentiation*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Kinases / physiology
  • Receptors, Cyclic AMP / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Signal Transduction


  • Calcium Channels
  • Cyclic AMP Response Element-Binding Protein
  • Receptors, Cyclic AMP
  • Receptors, N-Methyl-D-Aspartate
  • Cyclic AMP
  • Protein Kinases