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 Cγ1 (PLCG1), its etiological basis remains unclear. We report that mice lacking PLCγ1 in the forebrain (Plcg1f/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 γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII at inhibitory synapses. Moreover, mutant mice display impaired BDNF-TrkB-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 Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
- 2011-2012 Visiting Scholar, University of California, Berkeley, CA USA
- 2005-present Assistant, Associate, and Full Professorship, Pohang University of Science and Technology(POSTECH), Korea Mar.
- 2000-2005 Postdoctoral Research Scientist, Center for Neurobiology & Behavior, Columbia University, New York, NY USA Mar.
- 2001-2004 Howard Hughes Medical Institute(HHMI), New York, NY USA Mar.
- Neural correlates for animal behaviors
- Neural networks defining reward and emotional states
- Cellular and molecular mechanisms for synaptic plasticity
- Neurobiology group, Imperial College of Sciences, Technology & Medicine
- Ph.D. Mar. 2000 Neurobiology, University of London, London, UK
- M.S. Feb.1996 Medicine, College of Medicine, Seoul National University, Korea
- B.S. Feb. 1992 Microbiology, Seoul National University, Korea