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

Cell Reports
Stephen D GlasgowTimothy E Kennedy

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 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.

Citations

Apr 4, 2019·Journal of Veterinary Internal Medicine·Daisuke HasegawaMasaki Fukata
Dec 31, 2019·Journal of Neurochemistry·Matthias GrallePaul De Koninck
Jul 28, 2020·Frontiers in Cell and Developmental Biology·Santiago CuestaCecilia Flores
Feb 17, 2019·Learning & Memory·Edwin W WongTimothy E Kennedy
Aug 10, 2019·Frontiers in Synaptic Neuroscience·Stephen D GlasgowEdward S Ruthazer
Apr 9, 2020·Molecular Brain·Stephen D GlasgowTimothy E Kennedy
Jan 16, 2021·The Journal of Physiology·Derek Bowie
Jan 2, 2021·Biological Psychiatry·Angélica Torres-BerríoCecilia Flores
Apr 29, 2021·Neural Regeneration Research·Diane S Nakamura, Timothy E Kennedy

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