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    Synaptic connectivity within adult circuits exhibits a remarkable degree of cellular and subcellular specificity. We report that the axon guidance receptor Robo2 plays a role in establishing synaptic specificity in hippocampal CA1. In vivo, Robo2 is present and required postsynaptically in CA1 pyramidal neurons (PNs) for the formation of excitatory (E) but not inhibitory (I) synapses, specifically in proximal but not distal dendritic compartments. In vitro approaches show that the synaptogenic activity of Robo2 involves a trans-synaptic interaction with presynaptic Neurexins, as well as binding to its canonical extracellular ligand Slit. In vivo 2-photon Ca2+ imaging of CA1 PNs during spatial navigation in awake behaving mice shows that preventing Robo2-dependent excitatory synapse formation cell autonomously during development alters place cell properties of adult CA1 PNs. Our results identify a trans-synaptic complex linking the establishment of synaptic specificity to circuit function. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.


    Heike Blockus, Sebi V Rolotti, Miklos Szoboszlay, Eugénie Peze-Heidsieck, Tiffany Ming, Anna Schroeder, Nuno Apostolo, Kristel M Vennekens, Phinikoula S Katsamba, Fabiana Bahna, Seetha Mannepalli, Goran Ahlsen, Barry Honig, Lawrence Shapiro, Joris de Wit, Attila Losonczy, Franck Polleux. Synaptogenic activity of the axon guidance molecule Robo2 underlies hippocampal circuit function. Cell reports. 2021 Oct 19;37(3):109828

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    PMID: 34686348

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