| First Author | Papaleo F | Year | 2012 |
| Journal | Mol Psychiatry | Volume | 17 |
| Issue | 1 | Pages | 85-98 |
| PubMed ID | 20956979 | Mgi Jnum | J:244989 |
| Mgi Id | MGI:5913768 | Doi | 10.1038/mp.2010.106 |
| Citation | Papaleo F, et al. (2012) Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Mol Psychiatry 17(1):85-98 |
| abstractText | Dysbindin-1 regulates D2-receptor trafficking and is implicated in schizophrenia and related cognitive abnormalities, but whether this molecular effect mediates the clinical manifestations of the disorder is unknown. We explored in dysbindin-1-deficient mice (dys-/-) (1) schizophrenia-related behaviors, (2) molecular and electrophysiological changes in medial prefrontal cortex (mPFC) and (3) the dependence of these on D2-receptor stimulation. Dysbindin-1 disruption altered dopamine-related behaviors and impaired working memory under challenging/stressful conditions. Dys-/- pyramidal neurons in mPFC layers II/III were hyperexcitable at baseline but hypoexcitable following D2 stimulation. Dys-/- were also respectively more and less sensitive to D2 agonist- and antagonist-induced behavioral effects. Dys-/- had reduced expression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and CaMKKbeta in mPFC. Chronic D2 agonist treatment reproduced these changes in protein expression, and some of the dys-/- behavioral effects. These results elucidate dysbindin's modulation of D2-related behavior, cortical activity and mPFC CaMK components, implicating cellular and molecular mechanisms of the association of dysbindin with psychosis. |
