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

Kim, Seok‐Jin; Seo, Minsun; Kim, Duk‐Soo; Kang, Minji; Kim, Yeonsoo; Koh, Hun Yeong; Shin, Hee‐Sup

doi:10.1503/jpn.130285

Cited by 25 publications

(21 citation statements)

References 65 publications

(95 reference statements)

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“…The anxiogenic profile of Plcb1 +/− is in accordance with the results previously reported in the Plcb4 −/− mice, which were associated with alterations in the cholinergic activity of the medial septum [ 38 ]. However, the selective knock-down of Plcb1 in the mPFC did not replicate this phenotype in a previous study [ 39 ], suggesting that other areas may be involved. The anxiogenic profile of Plcb1 +/− mice had no effect on cocaine self-administration since the acquisition and extinction of this operant behavior was not modified in the mutants.…”

Section: Discussioncontrasting

confidence: 58%

Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/− mice

et al. 2021

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Cocaine addiction causes serious health problems, and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of the PLCB1 gene to cocaine addictive properties using Plcb1+/− mice. First, we performed a general phenotypic characterization and found that Plcb1+/− mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Subsequently, mice were trained for operant conditioning, self-administered cocaine for 10 days, and were tested for cocaine motivation. After extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/− mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/− mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation. To conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine-seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.

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Section: Discussioncontrasting

confidence: 58%

Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/− mice

et al. 2021

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“…mPFC neurons have also been reported to exhibit functional asymmetry between hemispheres in mice, such that the right mPFC was reported to control the acquisition of stress during hazardous experiences while the left mPFC was found to play a dominant role in translating stress into social behavior (Lee et al, 2016 ). Additionally, knockdown of phospholipase C-β1 in the mPFC impairs social interactions, whereas chronic deletion of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in the mPFC increases social approach behavior without affecting social novelty preference in mice (Finlay et al, 2015 ; Kim S. W. et al, 2015 ). NMDA-NR1 dysfunction in the CA3 region of the hippocampus is also sufficient to impair social approach, suggesting that social interaction can be differentially modulated by distinct alterations in a relevant circuit (Finlay et al, 2015 ).…”

Section: The Pfc and Related Network Areas Mediating Social Behaviormentioning

confidence: 99%

Neuroanatomical Substrates of Rodent Social Behavior: The Medial Prefrontal Cortex and Its Projection Patterns

2017

Front. Neural Circuits

180

126

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Social behavior encompasses a number of distinctive and complex constructs that form the core elements of human imitative culture, mainly represented as either affiliative or antagonistic interactions with conspecifics. Traditionally considered in the realm of psychology, social behavior research has benefited from recent advancements in neuroscience that have accelerated identification of the neural systems, circuits, causative genes and molecular mechanisms that underlie distinct social cognitive traits. In this review article, I summarize recent findings regarding the neuroanatomical substrates of key social behaviors, focusing on results from experiments conducted in rodent models. In particular, I will review the role of the medial prefrontal cortex (mPFC) and downstream subcortical structures in controlling social behavior, and discuss pertinent future research perspectives.

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“…Such conditions include Sterol regulatory element-binding protein 1c (SREBP1c) knockout (KO) mice [ 47 ], G protein-coupled receptor 88 (GPR88) KO mice [ 48 ], dystrobrevin binding protein 1 (Dtnbp1) deficiency mice [ 49 ], knockdown of metabotropic glutamate receptor 5 (mGluR 5) mice [ 50 ], N-methyl-D-aspartate (NMDA) receptor ablation mice [ 51 ], brain-specific collapsin response mediator protein 2 (CRMP2) KO mice [ 52 ], lq21.1 hemizygous microdeletion (hemizygotic Df(h1q21)/ +) mice + amphetamine [ 53 ], dopamine transporter (DAT) KO mice [ 54 ], and glial glutamate and aspartate transporter (GLAST) KO mice [ 55 ]. However, no effect on locomotor activity was observed in animal models with reduced solute carrier family 1 member 1 (SLC1A1) expression [ 56 ], growth arrest-specific 7 (GAS7) deficiency mice [ 57 ] (however, this model has decreased sensorimotor gating, as measured by PPI), type III neuregulin-1 (NRG1) +/− male mice from mutant fathers [ 58 ] (however, this model has increased sociability in the three-chamber test), and selective knockdown mice of phospholipase C-β1 (PLC-β1) in the medial prefrontal cortex (mPFC) [ 59 ]. Pharmacologically, several drugs, including amphetamine and MK-801 (NMDA receptor (NMDAR) antagonist) increase locomotor activity but can inversely lead to a decrease at higher doses due to sedative and anesthetic effects [ 23 ].…”

Section: Behavioral Tasks Measuring Positive Symptoms Of Schizophreniamentioning

confidence: 99%

Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update

Ang

Lee

Kim

et al. 2021

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Background: Schizophrenia is a serious mental illness that affects more than 21 million people worldwide. Both genetics and the environment play a role in its etiology and pathogenesis. Symptoms of schizophrenia are mainly categorized into positive, negative, and cognitive. One major approach to identify and understand these diverse symptoms in humans has been to study behavioral phenotypes in a range of animal models of schizophrenia. Objective: We aimed to provide a comprehensive review of the behavioral tasks commonly used for measuring schizophrenia-like behaviors in rodents together with an update of the recent study findings. Methods: Articles describing phenotypes of schizophrenia-like behaviors in various animal models were collected through a literature search in Google Scholar, PubMed, Web of Science, and Scopus, with a focus on advances over the last 10 years. Results: Numerous studies have used a range of animal models and behavioral paradigms of schizophrenia to develop antipsychotic drugs for improved therapeutics. In establishing animal models of schizophrenia, the candidate models were evaluated for schizophrenia-like behaviors using several behavioral tasks for positive, negative, and cognitive symptoms designed to verify human symptoms of schizophrenia. Such validated animal models were provided as rapid preclinical avenues for drug testing and mechanistic studies. Conclusion: Based on the most recent advances in the field, it is apparent that a myriad of behavior tests are needed to confirm and evaluate the congruency of animal models with the numerous behaviors and clinical signs exhibited by patients with schizophrenia

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

Cited by 25 publications

References 65 publications

Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/− mice

Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/− mice

Neuroanatomical Substrates of Rodent Social Behavior: The Medial Prefrontal Cortex and Its Projection Patterns

Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update

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