Long-term potentiation selectively expressed by NMDA receptors at hippocampal mossy fiber synapses

Neuron. 2008 Jan 10;57(1):108-20. doi: 10.1016/j.neuron.2007.11.024.


The mossy fiber to CA3 pyramidal cell synapse (mf-CA3) provides a major source of excitation to the hippocampus. Thus far, these glutamatergic synapses are well recognized for showing a presynaptic, NMDA receptor-independent form of LTP that is expressed as a long-lasting increase of transmitter release. Here, we show that in addition to this "classical" LTP, mf-CA3 synapses can undergo a form of LTP characterized by a selective enhancement of NMDA receptor-mediated transmission. This potentiation requires coactivation of NMDA and mGlu5 receptors and a postsynaptic calcium rise. Unlike classical LTP, expression of this mossy fiber LTP is due to a PKC-dependent recruitment of NMDA receptors specifically to the mf-CA3 synapse via a SNARE-dependent process. Having two mechanistically different forms of LTP may allow mf-CA3 synapses to respond with more flexibility to the changing demands of the hippocampal network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Radiation
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • GTP-Binding Proteins / deficiency
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Long-Term Potentiation / radiation effects
  • Mice
  • Mice, Knockout
  • Mossy Fibers, Hippocampal / physiology*
  • Patch-Clamp Techniques / methods
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptic Transmission / radiation effects
  • Synaptosomal-Associated Protein 25 / pharmacology


  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Rims1 protein, mouse
  • Synaptosomal-Associated Protein 25
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Egtazic Acid
  • GTP-Binding Proteins
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid