Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways

F. Papaleo, F. Yang, S. Garcia, J. Chen, B. Lu, J. N. Crawley, D. R. Weinberger

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


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 CaMKKΒ 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.

Original languageEnglish (US)
Pages (from-to)85-98
Number of pages14
JournalMolecular psychiatry
Issue number1
StatePublished - Jan 2012
Externally publishedYes


  • dopamine
  • genes
  • mice
  • prefrontal cortex
  • schizophrenia
  • working memory

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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