title: Regulation of dopamine D1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses.
abstract: 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.
authors.affiliation: Univ. de Bordeaux, Interdisciplinary Institute for Neuroscience, Unité Mixte de recherche UMR 5297, Bordeaux, France ; Centre National de la Recherche Scientifique CNRS, IINS UMR 5297, Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ladepeche
authors.forename: Luting
authors.initials: L
authors.lastname: Yang
authors.forename: Delphine
authors.initials: D
authors.lastname: Bouchet
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D018698:Glutamic Acid / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D057054:Molecular Imaging; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D057907:Post-Synaptic Density / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D045663:Quantum Dots; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
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