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TitleActivity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus.
Publication TypeJournal Article
Year of Publication2018
AuthorsGlasgow, Stephen D., Simon Labrecque, Ian V. Beamish, Sarah Aufmkolk, Julien Gibon, Dong Han, Stephanie N. Harris, Paul Dufresne, Paul W. Wiseman, Anne R McKinney, Philippe Séguéla, Paul De Koninck, Edward S. Ruthazer, and Timothy E. Kennedy
JournalCell Rep
Volume25
Issue1
Pagination168-182.e6
Date Published2018 Oct 02
ISSN2211-1247
Abstract

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, but 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. Furthermore, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca-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.

DOI10.1016/j.celrep.2018.09.028
Alternate JournalCell Rep
PubMed ID30282026