Netrin-1 Promotes Excitatory Synaptogenesis between Cortical Neurons by Initiating Synapse Assembly

• DOI: 10.1523/jneurosci.1085-13.2013
• Publication Date: 2013-10-30T16:49:11Z
• Authors: Jennifer S. Goldman; Mohammed A. Ashour; Margaret H. Magde...; Nicolas X. Tritsch; Stephanie N. Harris; Nicolas Christofi; Raja Chemali; Yaakov E. Stern; Greta Thompson-St...; Pavel Gris; Stephen D. Glasgow; Peter Grutter; Jean-Francois Bou...; Edward S. Ruthazer; David Stellwagen; Timothy E. Kennedy
• Keywords: Netrin; Synaptogenesis; Excitatory synapse

Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain postnatal period peak synapse formation. Here we demonstrate synaptogenic function netrin-1 rat mouse cortical neurons investigate underlying mechanism. We report its receptor DCC are widely by developing cortex enriched at synapses vivo . detect distributed along axons dendrites cultured provide evidence newly translated selectively transported dendrites. Using gain loss manipulations, increases number strength excitatory made between neurons. show complexity dendrite arbors, thereby increasing probability contact. At sites contact, promotes adhesion, while locally enriching reorganizing actin cytoskeleton through Src family kinase signaling m-Tor-dependent translation cluster presynaptic postsynaptic proteins. Finally, using whole-cell patch-clamp electrophysiology frequency amplitude mEPSCs recorded from pyramidal These findings identify as synapse-enriched synaptogenesis