A role for cAMP in long-term depression at hippocampal mossy fiber synapses

Neuron. 1998 Oct;21(4):837-45. doi: 10.1016/s0896-6273(00)80599-1.


Mossy fiber synapses on hippocampal CA3 pyramidal cells, in addition to expressing an NMDA receptor-independent form of long-term potentiation (LTP), have recently been shown to express a novel presynaptic form of long-term depression (LTD). We have studied the mechanisms underlying mossy fiber LTD and present evidence that it is triggered, at least in part, by a metabotropic glutamate receptor-mediated decrease in adenylyl cyclase activity, which leads to a decrease in the activity of the cAMP-dependent protein kinase (PKA) and a reversal of the presynaptic processes responsible for mossy fiber LTP. The bidirectional control of synaptic strength at mossy fiber synapses by activity therefore appears to be due to modulation of the cAMP-PKA signaling pathway in mossy fiber boutons.

Publication types

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

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Amino Acids, Dicarboxylic / pharmacology
  • Animals
  • Cyclic AMP / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Mice
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / physiology*
  • Receptors, Metabotropic Glutamate / physiology
  • Synapses / physiology*


  • Amino Acids, Dicarboxylic
  • Excitatory Amino Acid Agonists
  • Receptors, Metabotropic Glutamate
  • (alpha-carboxycyclopropyl)glycine
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases