Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region

Neuron. 1995 Dec;15(6):1403-14. doi: 10.1016/0896-6273(95)90018-7.


The role of the cAMP pathway in LTP was studied in the CA1 region of hippocampus. Widely spaced trains of high frequency stimulation generated cAMP postsynaptically via NMDA receptors and calmodulin, consistent with the Ca2+/calmodulin-mediated stimulation of postsynaptic adenylyl cyclase. The early phase of LTP produced by the same pattern of high frequency stimulation was dependent on postsynaptic cAMP. However, synaptic transmission was not increased by postsynaptic application of cAMP. Early LTP became cAMP-independent when protein phosphatase inhibitors were injected postsynaptically. These observations indicate that in early LTP the cAMP signaling pathway, instead of transmitting signals for the generation of LTP, gates LTP through postsynaptic protein phosphatases.

Publication types

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

MeSH terms

  • Animals
  • Calmodulin / physiology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism*
  • Cyclic AMP / pharmacology
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / physiology*
  • Ion Channel Gating*
  • Long-Term Potentiation*
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / metabolism*
  • Thionucleotides / pharmacology
  • Time Factors


  • Calmodulin
  • Enzyme Inhibitors
  • Receptors, N-Methyl-D-Aspartate
  • Thionucleotides
  • adenosine-3',5'-cyclic phosphorothioate
  • Cyclic AMP
  • Phosphoprotein Phosphatases