Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus.

TitleActivity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus.
Publication TypeJournal Article
Year of Publication2018
AuthorsGlasgow, SD, Labrecque, S, Beamish, IV, Aufmkolk, S, Gibon, J, Han, D, Harris, SN, Dufresne, P, Wiseman, PW, R McKinney, A, Séguéla, P, De Koninck, P, Ruthazer, ES, Kennedy, TE
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