Yang, Y. R. Jung, J. H. Kim, S-J Hamada, K. Suzuki, A. Kim, H. J. Lee, J. H. Kwon, O-B Lee, Y. K. Kim, J. Kim, E-K Jang, H-J Kang, D-S Choi, J-S Lee, C. J. Marshall, J. Koh, H-Y Kim, C-J Seok, H. Kim, S. H. Choi, J. H. Choi, Y-B Cocco, L. Ryu, S. H. Kim, J-H Suh, P-G 2024-01-20T00:31:58Z 2024-01-20T00:31:58Z 2021-09-04 2017-10 1359-4184 https://pubs.kist.re.kr/handle/201004/122243 Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase C gamma 1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase C gamma 1 (PLC gamma 1) in the forebrain (Plcg1(f/f); CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of gamma-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1(f/f); CaMKII mice. These findings provide evidence that PLC gamma 1 is critical for synaptic function and plasticity and that the loss of PLC gamma 1 from the forebrain results in manic-like behavior. English NATURE PUBLISHING GROUP LONG-TERM POTENTIATION BIPOLAR DISORDER SIGNALING PATHWAYS GABA(A) RECEPTORS NERVOUS-SYSTEM TRKB GENE BDNF HIPPOCAMPUS KINASE Forebrain-specific ablation of phospholipase C gamma 1 causes manic-like behavior Article 10.1038/mp.2016.261 1 MOLECULAR PSYCHIATRY, v.22, no.10, pp.1473 - 1482 MOLECULAR PSYCHIATRY 22 10 1473 1482 scie scopus 000411473400012 2-s2.0-85010931315 Biochemistry & Molecular Biology Neurosciences Psychiatry Biochemistry & Molecular Biology Neurosciences & Neurology Psychiatry Article LONG-TERM POTENTIATION BIPOLAR DISORDER SIGNALING PATHWAYS GABA(A) RECEPTORS NERVOUS-SYSTEM TRKB GENE BDNF HIPPOCAMPUS KINASE