Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo

Nat Neurosci. 2008 Feb;11(2):160-9. doi: 10.1038/nn2033. Epub 2008 Jan 13.

Abstract

Ephrin-Eph signaling is involved in axon guidance during development, but it may also regulate synapse development after the axon has contacted the target cell. Here we report that the activation of ephrin-B reverse signaling in the developing Xenopus laevis optic tectum promotes morphological and functional maturation of retinotectal synapses. Elevation of ephrin-B signaling increased the number of retinotectal synapses and stabilized the axon arbors of retinal ganglion cells. It also enhanced basal synaptic transmission and activity-induced long-term potentiation (LTP) of retinotectal synapses. The functional effects were caused by a rapid enhancement of presynaptic glutamate release and a delayed increase in the postsynaptic glutamate responsiveness. The facilitated LTP induction occurred during the early phase of enhanced transmitter release and appeared to be causally related to the late-phase postsynaptic maturation via an NMDA receptor-dependent mechanism. This ephrin-B-dependent synapse maturation supports the notion that the ephrin/Eph protein families have multiple functions in neural development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Axons / physiology
  • Electric Stimulation / methods
  • Ephrins / classification
  • Ephrins / pharmacology
  • Ephrins / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Green Fluorescent Proteins / metabolism
  • Long-Term Potentiation / physiology
  • Microscopy, Electron, Transmission
  • Neuronal Plasticity
  • Patch-Clamp Techniques / methods
  • Peptide Fragments / pharmacology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / physiology
  • Retinal Ganglion Cells / radiation effects
  • Signal Transduction / physiology*
  • Superior Colliculi / cytology
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Transmission / physiology*
  • Synaptosomal-Associated Protein 25 / metabolism
  • Time Factors
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • Xenopus laevis

Substances

  • Ephrins
  • Excitatory Amino Acid Antagonists
  • Peptide Fragments
  • Synaptosomal-Associated Protein 25
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-amino-5-phosphopentanoic acid
  • Valine