RT Journal Article SR Electronic T1 Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus JF bioRxiv FD Cold Spring Harbor Laboratory SP 330688 DO 10.1101/330688 A1 Stephen D. Glasgow A1 Simon Labrecque A1 Ian V. Beamish A1 Sarah Aufmkolk A1 Julien Gibon A1 Dong Han A1 Stephanie N. Harris A1 Paul Dufresne A1 Paul W. Wiseman A1 R. Anne McKinney A1 Philippe Séguéla A1 Paul De Koninck A1 Edward S. Ruthazer A1 Timothy E. Kennedy YR 2018 UL http://biorxiv.org/content/early/2018/05/25/330688.abstract AB Dynamic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.