Neuronal Activity and Intracellular Calcium Levels Regulate Intracellular Transport of Newly Synthesized AMPAR.

Hangen E, Cordelières FP, Petersen JD, Choquet D, Coussen F.
. 2018-08-24; 24(4): 1001-1012.e3
DOI: 10.1016/j.celrep.2018.06.095


Cell Rep. 2018 Jul 24;24(4):1001-1012.e3. doi: 10.1016/j.celrep.2018.06.095.

Neuronal Activity and Intracellular Calcium Levels Regulate Intracellular Transport of Newly Synthesized AMPAR.

Hangen E(1), Cordelières FP(2), Petersen JD(3), Choquet D(3), Coussen F(4).

(1) University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
(2) Bordeaux Imaging Center, UMS 3420 CNRS, US4 INSERM, University of Bordeaux, Bordeaux, France.
(3) University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; Bordeaux Imaging Center, UMS 3420 CNRS, US
(4) INSERM, University of Bordeaux, Bordeaux, France.4University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France. Electronic address: .

Abstract

Regulation of AMPA receptor (AMPAR) trafficking is a key modulator of excitatory synaptic transmission; however, intracellular vesicular transport of newly synthesized AMPARs has been little studied due to technical limitations. By combining molecular tools with imaging strategies in cultured rat hippocampal neurons, we found that vesicles containing newly synthesized, GluA1-subunit-containing AMPARs are transported antero- and retrogradely at a mean speed of 1.5 μm.s-1. Synaptic activity and variations in intracellular calcium levels bidirectionally modulate GluA1 transport. Chemical long-term potentiation (cLTP) initially induces a halt in GluA1 transport, followed by a sustained increase, while acute glutamate uncaging on synaptic spines arrests vesicular movements. GluA1 phosphomimetic mutants preferentially travel to the dendritic tip, probably to replenish extrasynaptic pools, distal to the soma. Our findings indicate that AMPAR intracellular transport is highly regulated during synaptic plasticity and likely controls AMPAR numbers at the plasma membrane.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

KEYWORDS:

GCaMP6f; GluA1-containing AMPARs; calcium; intracellular transport; long-term potentiation; phosphorylation; plasticity; synaptic activity; videomicroscopy

 


Auteurs Bordeaux Neurocampus