title: Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes.
abstract: BACKGROUND
  Decreased expression of phospholipase C-β1 (PLC-β1) has been observed in the brains of patients with schizophrenia, but, to our knowledge, no studies have shown a possible association between this altered PLC-β1 expression and the pathogenesis of schizophrenia. Although PLC-β1-null (PLC-β1(-/-)) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-β1 expression in the brain contribute to specific behavioural defects.
  
  
  METHODS
  We selectively knocked down PLC-β1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice.
  
  
  RESULTS
  Silencing PLC-β1 in the mPFC resulted in working memory deficits, as assayed using the delayed non-match-to-sample T-maze task. Notably, however, other schizophrenia-related behaviours observed in PLC-β1-/- mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-β1 knockdown mice.
  
  
  CONCLUSIONS
  Phenotypes of PLC-β1 knockdown mice, such as locomotion, anxiety and sensorimotor gating, have already been published in our previous studies. Further, the neural mechanisms underlying the working memory deficit in mice may be different from those in human schizophrenia.
  
  
  CONCLUSIONS
  These results indicate that PLC-β1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-β1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder.
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 305-811, and the Department of Neuroscience, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, and the Department of Neuroscience, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Misun
authors.initials: M
authors.lastname: Seo
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Republic of Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Indang Institute of Molecular Biology, Inje University, Seoul, Republic of Korea.
authors.forename: Moonkyung
authors.initials: M
authors.lastname: Kang
authors.affiliation: Indang Institute of Molecular Biology, Inje University, and the Department of Smart Foods and Drugs, Inje University, Seoul, Republic of Korea.
authors.forename: Yeon-Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul and the Department of Neuroscience, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Koh
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 305-811 and the Department of Neuroscience, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D004195:Disease Models, Animal; D058068:Endophenotypes; D055785:Gene Knockdown Techniques; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054799:Phospholipase C beta / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D065808:Prepulse Inhibition / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012919:Social Behavior
chemical_list: D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse