Role of Ca2+-stimulated adenylyl cyclases in LTP and memory formation

Int J Dev Neurosci. 2001 Jul;19(4):387-94. doi: 10.1016/s0736-5748(00)00094-0.


Studies with invertebrates and vertebrates have strongly implicated the CREB/CRE transcriptional pathway in long-term memory (LTM) and transcriptionally-dependent L-LTP. It is hypothesized that LTM and L-LTP are both dependent upon a Ca2+ signal generated through activation of NMDA receptors. This review discusses evidence that Ca2+ signals generated through activation of NMDA receptors coactivate the Erk/MAP kinase and cAMP signal transduction pathways. It is hypothesized that activation of these two regulatory pathways increases the transcription of a family of genes through the CREB/CRE transcriptional pathway. Gene disruption studies have shown that Ca2+ activated adenylyl cyclases play a critical role in generating the cAMP signal required for LTM and L-LTP. Although cAMP may be required for several events in this complex signal transduction cascade, one of the major roles of cAMP may be to support nuclear translocation of Erk/MAP kinase in hippocampal neurons.

Publication types

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

MeSH terms

  • Activating Transcription Factor 2
  • Active Transport, Cell Nucleus
  • Adenylyl Cyclases / physiology*
  • Animals
  • Calcium / physiology*
  • Calcium Signaling / physiology*
  • Circadian Rhythm / physiology
  • Cyclic AMP / physiology
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Enzyme Activation
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Long-Term Potentiation / physiology*
  • MAP Kinase Signaling System / physiology*
  • Memory / physiology*
  • Mice
  • Mossy Fibers, Hippocampal / physiology
  • Nerve Tissue Proteins / physiology*
  • Neurons / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors / physiology
  • Transcription, Genetic


  • Activating Transcription Factor 2
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Transcription Factors
  • Cyclic AMP
  • Adenylyl Cyclases
  • Calcium