Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses

Nature. 1995 Jul 20;376(6537):256-9. doi: 10.1038/376256a0.


Activity-dependent changes in synaptic strength are important for learning and memory. Long-term potentiation (LTP) of glutamatergic excitatory synapses following brief repetitive stimulation provides a compelling cellular model for such plasticity. In the CA1 region of the hippocampus, anatomical studies have revealed large numbers of NMDA (N-methyl-D-aspartate) receptor sites at excitatory synapses, which express primarily an NMDA receptor-dependent form of LTP. In contrast, these studies have suggested that mossy fibre synapses activate primarily or exclusively alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and, indeed, these synapses express a form of LTP that is entirely independent of NMDA receptors. Here we present physiological data demonstrating that mossy fibres activate a substantial NMDA receptor synaptic component that expresses LTP. The presence of an NMDA receptor response allowed us to use the open-channel NMDA receptor antagonist MK-801 to establish directly that the probability of transmitter release is enhanced during the expression of mossy fibre LTP.

Publication types

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

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Dizocilpine Maleate / pharmacology
  • Guinea Pigs
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Membrane Potentials
  • Nerve Fibers / physiology
  • Neurons, Afferent / physiology
  • Neurotransmitter Agents / metabolism
  • Pyramidal Cells / physiology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / physiology*
  • Synaptic Membranes / metabolism


  • Neurotransmitter Agents
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione