Journal article
Role of dysbindin in dopamine receptor trafficking and cortical GABA function
Proceedings of the National Academy of Sciences - PNAS, v 106(46), pp 19593-19598
17 Nov 2009
PMID: 19887632
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Abstract
Dysbindin has been implicated in the pathogenesis of schizophrenia, but little is known about how dysbindin affects neuronal function in the circuitry underlying psychosis and related behaviors. Using a
dysbindin
knockout line (dys
−/−
) derived from the natural
dysbindin
mutant Sandy mice, we have explored the role of dysbindin in dopamine signaling and neuronal function in the prefrontal cortex (PFC). Combined cell imaging and biochemical experiments revealed a robust increase in the dopamine receptor D2, but not D1, on cell surface of neurons from dys
−/−
cortex. This was due to an enhanced recycling and insertion, rather than reduced endocytosis, of D2. Disruption of
dysbindin
gene resulted in a marked decrease in the excitability of fast-spiking (FS) GABAergic interneurons in both PFC and striatum. Dys
−/−
mice also exhibited a decreased inhibitory input to pyramidal neurons in layer V of PFC. The increased D2 signaling in dys
−/−
FS interneurons was associated with a more pronounced increase in neuronal firing in response to D2 agonist, compared to that in wild-type interneurons. Taken together, these results suggest that dysbindin regulates PFC function by facilitating D2-mediated modulation of GABAergic function.
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Details
- Title
- Role of dysbindin in dopamine receptor trafficking and cortical GABA function
- Creators
- Yuanyuan Ji - Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, MD 20892Feng Yang - Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, MD 20892Francesco Papaleo - Genes, Cognition and Psychosis Program, National Institute of Mental Health, Bethesda, MD 20892; andHuai-Xing Wang - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129Wen-Jun Gao - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129Daniel R Weinberger - Genes, Cognition and Psychosis Program, National Institute of Mental Health, Bethesda, MD 20892; andBai Lu - Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, MD 20892
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 106(46), pp 19593-19598
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000271907400066
- Scopus ID
- 2-s2.0-73349091579
- Other Identifier
- 991014878418404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences