title: Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning.
abstract: Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.
authors.affiliation: Neuroscience Group, Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, South Dakota 57069, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Zheng
authors.forename: Joyce
authors.initials: J
authors.lastname: Keifer
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D015153:Blotting, Western; D001933:Brain Stem / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003056:Cochlear Nerve / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D036387:Ephrin-B1 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047468:Immunoprecipitation; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions; D013569:Synapses / Q000378:metabolism*; D014426:Turtles
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D036387:Ephrin-B1; D036081:Receptors, Eph Family; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases