cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase

Cell. 1994 Oct 7;79(1):69-79. doi: 10.1016/0092-8674(94)90401-4.


Memory storage has a short-term phase that depends on preexisting proteins and a long-term phase that requires new protein and RNA synthesis. Hippocampal long-term potentiation (LTP) is thought to contribute to memory storage. Consistent with this idea, a cellular representation of these phases has been demonstrated in NMDA receptor-dependent LTP. By contrast, little is known about the NMDA receptor-independent LTP of the mossy fiber pathway. We find that mossy fiber LTP also has phases. Only late phase is blocked by protein and RNA synthesis inhibitors, but both phases are blocked by inhibitors of cAMP-dependent protein kinase, and both are stimulated by forskolin and Sp-cAMPS. During early phase, paired-pulse facilitation is occluded. This occlusion decays with the onset of late phase, consistent with its using a different mechanism. Thus, although Schaffer collateral and mossy fiber pathways use very different mechanisms for early phase, both use a cAMP-mediated mechanism for late phase.

Publication types

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

MeSH terms

  • Animals
  • Anisomycin / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / pharmacology
  • Cyclic AMP / physiology*
  • Dactinomycin / pharmacology
  • Electric Stimulation
  • Hippocampus / metabolism
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Nerve Fibers / physiology*
  • Nerve Tissue Proteins / biosynthesis
  • Protein Kinase Inhibitors
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Retention, Psychology / physiology*
  • Second Messenger Systems / drug effects
  • Thionucleotides / pharmacology


  • Nerve Tissue Proteins
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • Thionucleotides
  • Dactinomycin
  • Colforsin
  • adenosine-3',5'-cyclic phosphorothioate
  • Anisomycin
  • Cyclic AMP