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| Content Provider | PubMed Central |
|---|---|
| Author | Jentsch, J. David Heather, Trantham-davidson Corey, Jairl Tinsley, Matthew Cannon, Tyrone D. Lavin, Antonieta |
| Abstract | Behavioral genetic studies of humans have associated variation in the DTNBP1 gene with schizophrenia and its cognitive deficit phenotypes. The protein coded for by DTNBP1, dysbindin, is expressed within forebrain glutamatergic neurons, where it interacts with proteins involved in vesicular trafficking and exocytosis. In order to further delineate the cellular, physiological and behavioral phenotypes associated with reduced dysbindin expression, we conducted studies in mice carrying a null mutation within the dtnbp1 gene. Dysbindin mutants exhibited impairments of spatial working memory as compared with wild-type controls; heterozygous mice exhibited intermediate levels of cognitive dysfunction. Deep layer pyramidal neurons recorded in the prefrontal cortex of mutant mice exhibited reductions in paired-pulse facilitation, and evoked and miniature excitatory post-synaptic currents, indicating a difference in the function of pre-synaptic glutamatergic terminals, as well as elevated spike thresholds. Taken together, these data indicate that dysbindin potently regulates excitatory transmission in prefrontal cortex, potentially through a pre-synaptic mechanism, and consequently modulates cognitive functions depending upon this brain region, providing new insights into the molecular mechanisms underlying cortical dysfunction in schizophrenia. |
| Related Links | http://dx.doi.org/10.1038/npp.2009.90 |
| Ending Page | 2608 |
| Page Count | 8 |
| Starting Page | 2601 |
| File Format | |
| ISSN | 0893133X |
| e-ISSN | 1740634X |
| Journal | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology |
| Issue Number | 12 |
| Volume Number | 34 |
| Language | English |
| Publisher Date | 2009-11-01 |
| Access Restriction | Open |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Psychiatry and Mental Health |
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