| First Author | Kim SW | Year | 2015 |
| Journal | J Psychiatry Neurosci | Volume | 40 |
| Issue | 2 | Pages | 78-88 |
| PubMed ID | 25268789 | Mgi Jnum | J:258958 |
| Mgi Id | MGI:6140938 | Doi | 10.1503/jpn.130285 |
| Citation | Kim SW, et al. (2015) Knockdown of phospholipase C-beta1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes. J Psychiatry Neurosci 40(2):78-88 |
| abstractText | BACKGROUND: Decreased expression of phospholipase C-beta1 (PLC-beta1) 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-beta1 expression and the pathogenesis of schizophrenia. Although PLC-beta1-null (PLC-beta1(-/-)) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-beta1 expression in the brain contribute to specific behavioural defects. METHODS: We selectively knocked down PLC-beta1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice. RESULTS: Silencing PLC-beta1 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-beta1-/- mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-beta1 knockdown mice. LIMITATIONS: Phenotypes of PLC-beta1 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. CONCLUSION: These results indicate that PLC-beta1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-beta1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder. |
