Deficits in social behavior and sensorimotor gating in mice lacking phospholipase Cβ1

Abstract

Abnormal phospholipid metabolism has been implicated in the pathogenesis of schizophrenia, and it was reported that phospholipase C (PLC) b1 is reduced in specific brain areas of patients with schizophrenia. However, the causal relationship of the PLCb1 gene with behavioral symptoms of schizophrenia remains unclear. To address this issue, we have examined the mutant mice lacking PLCb1 for schizophrenia-related phenotypes by performing various behavioral tests, including general locomotor activity, sensorimotor gating, social behaviors, and learning and memory. Phospholipase C b1 knockout mice showed hyperactivities in an open field. They showed impaired prepulse inhibition of acoustic startle response, which was ameliorated by a systemic administration of an antipsychotic D2-receptor antagonist, haloperidol. In addition, they showed abnormal social behaviors, such as lack of barbering behavior, socially recessive trait and lack of nesting behavior. Furthermore, they showed impaired performance in the delayed-nonmatch-to-sample T-maze test. The present results show that the PLCb1 mutant mice share some of the behavioral abnormalities that have been reported in patients with schizophrenia. Thus, the PLCb1-linked signaling pathways may be involved in the neural system whose function is disrupted in the pathogenesis of schizophrenia.

Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes

“…10,12 In the openfield assay, shPLCβ1injected mice showed no significant difference in the total amount of locomotor activity in the open field com pared with shSCR and vehicle (phosphatebuffered saline)-injected mice (F 2,28 = 0.317, p = 0.73; Fig. 3A and B).…”

“…Other behavioural phenotypes of PLCβ1 -/-mice, such as openfield, DNMTS Tmaze, PPI, elevated plusmaze, and a light/dark transition task, have already been published in our previous studies, 10,12 and these behavioural tests of mPFCspecific PLCβ1 knockdown mice were performed under the same experimental conditions as performed previ ously with PLCβ1 -/-mice. On the other hand, the sociability test was not done for the PLCβ1 -/-mice previously.…”

“…3,7,8 Several studies have previously reported that PLCβ1related pathways are involved in various neurophysiological func tions. 4,[9][10][11][12] Moreover, decreased expression of PLCβ1 has been detected in the brains of patients with schizophrenia. [13][14][15][16][17][18] Schizophrenia symptoms are categorized into 3 major types 19,20 -positive, negative and cognitive -and a majority of these symptoms have been observed as endophenotypes in PLCβ1null (PLCβ1 −/− ) mice.…”

“…[13][14][15][16][17][18] Schizophrenia symptoms are categorized into 3 major types 19,20 -positive, negative and cognitive -and a majority of these symptoms have been observed as endophenotypes in PLCβ1null (PLCβ1 −/− ) mice. [9][10][11][12] These symptoms include increased locomotion, impaired social behaviour, impaired prepulse inhibition (PPI), and impaired working memory. [9][10][11][12] Furthermore, reports of altered PLCβ1 expression in the brains of patients with schizophrenia, such as in the dorsolat eral prefrontal cortex (DLPFC), have suggested the possible pathogenic involvement of PLCβ1 in schizophrenia.…”

“…[9][10][11][12] These symptoms include increased locomotion, impaired social behaviour, impaired prepulse inhibition (PPI), and impaired working memory. [9][10][11][12] Furthermore, reports of altered PLCβ1 expression in the brains of patients with schizophrenia, such as in the dorsolat eral prefrontal cortex (DLPFC), have suggested the possible pathogenic involvement of PLCβ1 in schizophrenia.…”