Synaptogenic activity of the axon guidance molecule Robo2 underlies hippocampal circuit function
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
DYNAMICS
synaptic specificity Mice 129 Strain SYNAPSES dendrites QH301-705.5 MIGRATION DEVELOPMENTAL MECHANISMS INHIBITION Nerve Tissue Proteins Article DOMAIN Animals Humans Receptors Immunologic Biology (General) CA1 Region Hippocampal Neural Cell Adhesion Molecules Mice Knockout Science & Technology neurexins Pyramidal Cells Calcium-Binding Proteins CORTICAL-NEURONS Excitatory Postsynaptic Potentials Slit-Robo Cell Biology CA3 Region Hippocampal Mice Inbred C57BL RECEPTORS HEK293 Cells SYNAPTIC-TRANSMISSION Place Cells nervous system Synapses CELLS Intercellular Signaling Peptides and Proteins synapse development Life Sciences & Biomedicine synaptic adhesion molecules |
| Zdroj: | Cell Reports, Vol 37, Iss 3, Pp 109828-(2021) Cell reports |
| Popis: | SUMMARY 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. In brief Blockus et al. demonstrate that the axon guidance receptors Robo1/2 are synaptogenic cues required postsynaptically for the establishment of synaptic specificity between CA3 axons and dendrites of CA1 pyramidal neurons (PNs). Developmental deletion of Robo2 in CA1 PNs disrupts the emergence of place cell properties in adult hippocampus. Graphical Abstract |
| Databáze: | OpenAIRE |
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