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Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity.

Neuron | 2004

To identify the molecular mechanisms underlying psychostimulant-elicited plasticity in the brain reward system, we undertook a phenotype-driven approach using genome-wide microarray profiling of striatal transcripts from three genetic and one pharmacological mouse models of psychostimulant or dopamine supersensitivity. A small set of co-affected genes was identified. One of these genes encoding the synaptic scaffolding protein PSD-95 is downregulated in the striatum of all three mutants and in chronically, but not acutely, cocaine-treated mice. At the synaptic level, enhanced long-term potentiation (LTP) of the frontocortico-accumbal glutamatergic synapses correlates with PSD-95 reduction in every case. Finally, targeted deletion of PSD-95 in an independent line of mice enhances LTP, augments the acute locomotor-stimulating effects of cocaine, but leads to no further behavioral plasticity in response to chronic cocaine. Our findings uncover a previously unappreciated role of PSD-95 in psychostimulant action and identify a molecular and cellular mechanism shared between drug-related plasticity and learning.

Pubmed ID: 14980210 RIS Download

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Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: DA13511

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Gene Ontology (tool)

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Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.

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Functional Genomics Data Society (tool)

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THIS RESOURCE IS NO LONGER IN SERVICE.Documented on July 7, 2022. Functional Genomics Data Society - FGED Society, founded in 1999 as the MGED Society, advocates for open access to genomic data sets and works towards providing concrete solutions to achieve this. Our goal is to assure that investment in functional genomics data generates the maximum public benefit. Our work on defining minimum information specifications for reporting data in functional genomics papers have already enabled large data sets to be used and reused to their greater potential in biological and medical research. We work with other organizations to develop standards for biological research data quality, annotation and exchange. We facilitate the creation and use of software tools that build on these standards and allow researchers to annotate and share their data easily. We promote scientific discovery that is driven by genome wide and other biological research data integration and meta-analysis.

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