McOmish, C. E. Burrows, E. Howard, M. Scarr, E. Kim, D. Shin, H-S Dean, B. van den Buuse, M. Hannan, A. J. 2024-01-20T23:02:51Z 2024-01-20T23:02:51Z 2021-09-03 2008-07 1359-4184 https://pubs.kist.re.kr/handle/201004/133350 Phospholipase C-beta 1 (PLC-beta 1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-beta 1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-beta 1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenia-like symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-beta 1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions. English NATURE PUBLISHING GROUP MUSCARINIC ACETYLCHOLINE-RECEPTOR BRAIN CORTICAL MEMBRANES SUPERIOR TEMPORAL CORTEX WORKING-MEMORY DEFICITS ACOUSTIC STARTLE REFLEX PREPULSE INHIBITION NEUROTRANSMITTER RECEPTORS GLUTAMATE RECEPTORS ANTIPSYCHOTIC-DRUGS PREFRONTAL CORTEX Phospholipase C-beta 1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration Article 10.1038/sj.mp.4002046 1 MOLECULAR PSYCHIATRY, v.13, no.7, pp.661 - 672 MOLECULAR PSYCHIATRY 13 7 661 672 scie scopus 000256832700005 2-s2.0-45549107762 Biochemistry & Molecular Biology Neurosciences Psychiatry Biochemistry & Molecular Biology Neurosciences & Neurology Psychiatry Article MUSCARINIC ACETYLCHOLINE-RECEPTOR BRAIN CORTICAL MEMBRANES SUPERIOR TEMPORAL CORTEX WORKING-MEMORY DEFICITS ACOUSTIC STARTLE REFLEX PREPULSE INHIBITION NEUROTRANSMITTER RECEPTORS GLUTAMATE RECEPTORS ANTIPSYCHOTIC-DRUGS PREFRONTAL CORTEX schizophrenia muscarinic receptors environmental enrichment antipsychotics clozapine haloperidol