B-ephrin reverse signaling is required for NMDA-independent long-term potentiation of mossy fibers in the hippocampus

John N. Armstrong, Michael J. Saganich, Nan Jie Xu, Mark Henkemeyer, Stephen F. Heinemann, Anis Contractor

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The mossy fiber to CA3 pyramidal neuron synapse in the hippocampus displays an atypical form of NMDA receptor-independent long-term potentiation (LTP). Plasticity at this synapse is expressed in the presynaptic terminal as an elevated probability of neurotransmitter release. However, evidence indicates that postsynaptic mechanisms and trans-synaptic signaling through an association between postsynaptic EphB receptors and presynaptic B-ephrins are necessary for the induction of LTP. Here we show that ephrin-B3 protein is highly expressed in mossy fiber axons and terminals. There are specific deficits in mossy fiber LTP in mice in which the cytoplasmic C-terminal signaling domain of the ephrin-B3 protein is replaced with β-galactosidase. These deficits are not observed in ephrin-B3 null mutant mice because of functional redundancy by virtue of other B-ephrins. These results indicate that B-ephrin reverse signaling into the presynaptic mossy fiber bouton is required for the induction of NMDA receptor-independent LTP at this synapse.

Original languageEnglish (US)
Pages (from-to)3474-3481
Number of pages8
JournalJournal of Neuroscience
Issue number13
StatePublished - Mar 29 2006



  • Ephrin
  • Hippocampus
  • Long-term potentiation
  • Mossy fiber
  • Presynaptic signaling
  • Pyramidal neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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