Journal article
Distinct roles for spinophilin and neurabin in dopamine-mediated plasticity
Neuroscience, v 140(3), pp 897-911
2006
PMID: 16600521
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Protein phosphatase 1 plays a major role in the governance of excitatory synaptic activity, and is subject to control via the neuromodulatory actions of dopamine. Mechanisms involved in regulating protein phosphatase 1 activity include interactions with the structurally related cytoskeletal elements spinophilin and neurabin, synaptic scaffolding proteins that are highly enriched in dendritic spines. The requirement for these proteins in dopamine-related neuromodulation was tested using knockout mice. Dopamine D1-mediated regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor activity was deficient in both striatal and prefrontal cortical neurons from neurabin knockout mice; in spinophilin knockout mice this deficit was manifest only in striatal neurons. At corticostriatal synapses long-term potentiation was deficient in neurabin knockout mice, but not in spinophilin knockout mice, and was rescued by a D1 receptor agonist. In contrast, long-term depression was deficient in spinophilin knockout mice but not in neurabin knockout mice, and was rescued by D2 receptor activation. Spontaneous excitatory post-synaptic current frequency was increased in neurabin knockout mice, but not in spinophilin knockout mice, and this effect was normalized by D2 receptor agonist application. Both knockout strains displayed increased induction of GluR1 Ser
845 phosphorylation in response to D1 receptor stimulation in slices, and also displayed enhanced locomotor activation in response to cocaine administration. These effects could be dissociated from cocaine reward, which was enhanced only in spinophilin knockout mice, and was accompanied by increased immediate early gene induction. These data establish a requirement for synaptic scaffolding in dopamine-mediated responses, and further indicate that spinophilin and neurabin play distinct roles in dopaminergic signal transduction and psychostimulant response.
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Details
- Title
- Distinct roles for spinophilin and neurabin in dopamine-mediated plasticity
- Creators
- P.B. Allen - Yale UniversityV. Zachariou - University of CreteP. Svenningsson - Karolinska InstituteA.C. Lepore - Drexel UniversityD. Centonze - University of Rome Tor VergataC. Costa - University of Rome Tor VergataS. Rossi - University of Rome Tor VergataG. Bender - Yale UniversityG. Chen - University at Buffalo, State University of New YorkJ. Feng - University at Buffalo, State University of New YorkG.L. Snyder - Drexel UniversityG. Bernardi - University of Rome Tor VergataE.J. Nestler - The University of Texas Southwestern Medical CenterZ. Yan - University at Buffalo, State University of New YorkP. Calabresi - University of PerugiaP. Greengard - Rockefeller University
- Publication Details
- Neuroscience, v 140(3), pp 897-911
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Health Sciences
- Web of Science ID
- WOS:000238232000015
- Scopus ID
- 2-s2.0-33646762500
- Other Identifier
- 991019168707404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences