B-ephrin reverse signaling is required for NMDA-independent long-term potentiation of mossy fibers in the hippocampus.
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 beta-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.
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 93037, USA.
John N
JN
Armstrong
Michael J
MJ
Saganich
Nan-Jie
NJ
Xu
Mark
M
Henkemeyer
Stephen F
SF
Heinemann
Anis
A
Contractor
D000818:Animals; D002478:Cells, Cultured; D036389:Ephrin-B3 / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D016202:N-Methylaspartate / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D036389:Ephrin-B3; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate