title: Robo3-driven axon midline crossing conditions functional maturation of a large commissural synapse.
abstract: During the formation of neuronal circuits, axon pathfinding decisions specify the location of synapses on the correct brain side and in correct target areas. We investigated a possible link between axon midline crossing and the subsequent development of output synapses formed by these axons. Conditional knockout of Robo3 in the auditory system forced a large commissural synapse, the calyx of Held, to be exclusively formed on the wrong, ipsilateral side. Ipsilateral calyx of Held synapses showed strong transmission defects, with reduced and desynchronized transmitter release, fewer fast-releasable vesicles, and smaller and more variable presynaptic Ca(2+) currents. Transmission defects were not observed in a downstream inhibitory synapse, and some defects persisted into adulthood. These results suggest that axon midline crossing conditions functional maturation of commissural synapses, thereby minimizing the impact of mislocalized synapses on information processing. This mechanism might be relevant to human disease caused by mutations in the ROBO3 gene.
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Michalski
authors.forename: Norbert
authors.initials: N
authors.lastname: Babai
authors.forename: Nicolas
authors.initials: N
authors.lastname: Renier
authors.forename: David J
authors.initials: DJ
authors.lastname: Perkel
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
authors.forename: Ralf
authors.initials: R
authors.lastname: Schneggenburger
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001306:Auditory Pathways / Q000502:physiology; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001703:Biophysics; D001933:Brain Stem / Q000166:cytology*; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D051767:Early Growth Response Protein 2 / Q000235:genetics; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011956:Receptors, Cell Surface; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D002586:Cesium; D002712:Chlorides; D051767:Early Growth Response Protein 2; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D016760:Proto-Oncogene Proteins c-fos; D011956:Receptors, Cell Surface; D050599:Vesicular Glutamate Transport Protein 2; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C028019:cesium chloride