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Robo3-Driven Axon Midline Crossing Conditions Functional Maturation of a Large Commissural Synapse

Abstract : During the formation of neuronal circuits, axon path-finding 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 desynchron-ized transmitter release, fewer fast-releasable vesi-cles, 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 synap-ses on information processing. This mechanism might be relevant to human disease caused by mutations in the ROBO3 gene.
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Nicolas Michalski, Norbert Babai, Nicolas Renier, David j. Perkel, Alain Chédotal, et al.. Robo3-Driven Axon Midline Crossing Conditions Functional Maturation of a Large Commissural Synapse. Neuron, Elsevier, 2013, 78 (5), pp.855 - 868. ⟨10.1016/j.neuron.2013.04.006⟩. ⟨pasteur-01472841⟩

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