title: EphA4 signaling in juveniles establishes topographic specificity of structural plasticity in the hippocampus.
abstract: The formation and loss of synapses is involved in learning and memory. Distinct subpopulations of permanent and plastic synapses coexist in the adult brain, but the principles and mechanisms underlying the establishment of these distinctions remain unclear. Here we show that in the hippocampus, terminal arborizations (TAs) with high plasticity properties are specified at juvenile stages, and account for most synapse turnover of adult mossy fibers. Out of 9-12 giant terminals along CA3, distinct subpopulations of granule neurons revealed by mouse reporter lines exhibit 0, 1, or >2 TAs. TA specification involves a topographic rule based on cell body position and EphA4 signaling. Upon disruption of EphA4 signaling or PSA-NCAM in juvenile circuits, single-TA mossy fibers establish >2 TAs, suggesting that intra-axonal competition influences plasticity site selection. Therefore, plastic synapse specification in juveniles defines sites of synaptic remodeling in the adult, and hippocampal circuit plasticity follows unexpected topographic principles.
authors.affiliation: Friedrich Miescher Institut, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Galimberti
authors.forename: Ewa
authors.initials: E
authors.lastname: Bednarek
authors.forename: Flavio
authors.initials: F
authors.lastname: Donato
authors.forename: Pico
authors.initials: P
authors.lastname: Caroni
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D001931:Brain Mapping; D001973:Bromodeoxyuridine / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: C498441:Bsn protein, mouse; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D049452:Green Fluorescent Proteins; D036122:Receptor, EphA4; D001973:Bromodeoxyuridine