Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors.

Details

Serval ID
serval:BIB_34AD8C20A6CB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors.
Journal
Neuron
Author(s)
Yuan T., Mameli M., O'Connor E.C., Dey P.N., Verpelli C., Sala C., Perez-Otano I., Lüscher C., Bellone C.
ISSN
1097-4199 (Electronic)
ISSN-L
0896-6273
Publication state
Published
Issued date
20/11/2013
Peer-reviewed
Oui
Volume
80
Number
4
Pages
1025-1038
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: epublish
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Drug-evoked synaptic plasticity in the mesolimbic dopamine (DA) system reorganizes neural circuits that may lead to addictive behavior. The first cocaine exposure potentiates AMPAR excitatory postsynaptic currents (EPSCs) onto DA neurons of the VTA but reduces the amplitude of NMDAR-EPSCs. While plasticity of AMPAR transmission is expressed by insertion of calcium (Ca(2+))-permeable GluA2-lacking receptors, little is known about the expression mechanism for altered NMDAR transmission. Combining ex vivo patch-clamp recordings, mouse genetics, and subcellular Ca(2+) imaging, we observe that cocaine drives the insertion of NMDARs that are quasi-Ca(2+)-impermeable and contain GluN3A and GluN2B subunits. These GluN3A-containing NMDARs appear necessary for the expression of cocaine-evoked plasticity of AMPARs. We identify an mGluR1-dependent mechanism to remove these noncanonical NMDARs that requires Homer/Shank interaction and protein synthesis. Our data provide insight into the early cocaine-driven reorganization of glutamatergic transmission onto DA neurons and offer GluN3A-containing NMDARs as new targets in drug addiction.

Keywords
Animals, Behavior, Animal/drug effects, Calcium/metabolism, Cocaine/pharmacology, Dopamine Uptake Inhibitors/pharmacology, Dopaminergic Neurons/drug effects, Excitatory Postsynaptic Potentials/drug effects, Female, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Microinjections, Neuronal Plasticity/drug effects, Patch-Clamp Techniques, RNA Interference, Receptors, AMPA/drug effects, Receptors, N-Methyl-D-Aspartate/drug effects, Receptors, N-Methyl-D-Aspartate/metabolism, Receptors, N-Methyl-D-Aspartate/physiology, Signal Transduction/drug effects, Stereotaxic Techniques, Synapses/drug effects, Synaptic Transmission/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2017 15:02
Last modification date
20/08/2019 13:21
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