title: Single-molecule imaging of the functional crosstalk between surface NMDA and dopamine D1 receptors.
abstract: Dopamine is a powerful modulator of glutamatergic neurotransmission and NMDA receptor-dependent synaptic plasticity. Although several intracellular cascades participating in this functional dialogue have been identified over the last few decades, the molecular crosstalk between surface dopamine and glutamate NMDA receptor (NMDAR) signaling still remains poorly understood. Using a combination of single-molecule detection imaging and electrophysiology in live hippocampal neurons, we demonstrate here that dopamine D1 receptors (D1Rs) and NMDARs form dynamic surface clusters in the vicinity of glutamate synapses. Strikingly, D1R activation or D1R/NMDAR direct interaction disruption decreases the size of these clusters, increases NMDAR synaptic content through a fast lateral redistribution of the receptors, and favors long-term synaptic potentiation. Together, these data demonstrate the presence of dynamic D1R/NMDAR perisynaptic reservoirs favoring a rapid and bidirectional surface crosstalk between receptors and set the plasma membrane as the primary stage of the dopamine-glutamate interplay.
authors.affiliation: Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche (UMR) 5297, Université de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ladepeche
authors.forename: Julien P
authors.initials: JP
authors.lastname: Dupuis
authors.forename: Delphine
authors.initials: D
authors.lastname: Bouchet
authors.forename: Evelyne
authors.initials: E
authors.lastname: Doudnikoff
authors.forename: Luting
authors.initials: L
authors.lastname: Yang
authors.forename: Yohan
authors.initials: Y
authors.lastname: Campagne
authors.forename: Erwan
authors.initials: E
authors.lastname: Bézard
authors.forename: Eric
authors.initials: E
authors.lastname: Hosy
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008959:Models, Neurological; D053758:Nanoparticles; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*
chemical_list: D017447:Receptors, Dopamine D1; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate
keywords: glutamate plasticity; hippocampus; neuromodulation; receptor diffusion; single-molecule tracking