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Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses

Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signa...

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Autores principales: Ladepeche, Laurent, Yang, Luting, Bouchet, Delphine, Groc, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765443/
https://www.ncbi.nlm.nih.gov/pubmed/24040266
http://dx.doi.org/10.1371/journal.pone.0074512
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author Ladepeche, Laurent
Yang, Luting
Bouchet, Delphine
Groc, Laurent
author_facet Ladepeche, Laurent
Yang, Luting
Bouchet, Delphine
Groc, Laurent
author_sort Ladepeche, Laurent
collection PubMed
description Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR) have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R) laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk.
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spelling pubmed-37654432013-09-13 Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses Ladepeche, Laurent Yang, Luting Bouchet, Delphine Groc, Laurent PLoS One Research Article Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR) have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R) laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk. Public Library of Science 2013-09-06 /pmc/articles/PMC3765443/ /pubmed/24040266 http://dx.doi.org/10.1371/journal.pone.0074512 Text en © 2013 Ladepeche et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ladepeche, Laurent
Yang, Luting
Bouchet, Delphine
Groc, Laurent
Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses
title Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses
title_full Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses
title_fullStr Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses
title_full_unstemmed Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses
title_short Regulation of Dopamine D1 Receptor Dynamics within the Postsynaptic Density of Hippocampal Glutamate Synapses
title_sort regulation of dopamine d1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765443/
https://www.ncbi.nlm.nih.gov/pubmed/24040266
http://dx.doi.org/10.1371/journal.pone.0074512
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