Calsyntenin-1 regulates targeting of dendritic NMDA receptors and dendritic spine maturation in CA1 hippocampal pyramidal cells during postnatal development

• Published in: The Journal of neuroscience 2014-06, Vol.34 (26), p.8716-8727
• Main Authors: Ster, Jeanne, Steuble, Martin, Orlando, Clara, Diep, Tu-My, Akhmedov, Alexander, Raineteau, Olivier, Pernet, Vincent, Sonderegger, Peter, Gerber, Urs
• Format: Article
• Language: English
• Subjects: Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - growth & development; CA1 Region, Hippocampal - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Dendrites - metabolism; Dendritic Spines - metabolism; Excitatory Postsynaptic Potentials - physiology; Mice; Mice, Knockout; Pyramidal Cells - cytology; Pyramidal Cells - growth & development; Pyramidal Cells - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Synapses - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.0144-14.2014

Calsyntenin-1 is a transmembrane cargo-docking protein important for kinesin-1-mediated fast transport of membrane-bound organelles that exhibits peak expression levels at postnatal day 7. However, its neuronal function during postnatal development remains unknown. We generated a knock-out mouse to characterize calsyntenin-1 function in juvenile mice. In the absence of calsyntenin-1, synaptic transmission was depressed. To address the mechanism, evoked EPSPs were analyzed revealing a greater proportion of synaptic GluN2B subunit-containing receptors typical for less mature synapses. This imbalance was due to a disruption in calsyntenin-1-mediated dendritic transport of NMDA receptor subunits. As a consequence of increased expression of GluN2B subunits, NMDA receptor-dependent LTP was enhanced at Schaffer collateral-CA1 pyramidal cell synapses. Interestingly, these defects were accompanied by a decrease in dendritic arborization and increased proportions of immature filopodia-like dendritic protrusions at the expense of thin-type dendritic spines in CA1 pyramidal cells. Thus, these results highlight a key role for calsyntenin-1 in the transport of NMDA receptors to synaptic targets, which is necessary for the maturation of neuronal circuits during early development.