title: Impaired limbic gamma oscillatory synchrony during anxiety-related behavior in a genetic mouse model of bipolar mania.
abstract: Alterations in anxiety-related processing are observed across many neuropsychiatric disorders, including bipolar disorder. Though polymorphisms in a number of circadian genes confer risk for this disorder, little is known about how changes in circadian gene function disrupt brain circuits critical for anxiety-related processing. Here we characterize neurophysiological activity simultaneously across five limbic brain areas (nucleus accumbens, amygdala, prelimbic cortex, ventral hippocampus, and ventral tegmental area) as wild-type (WT) mice and mice with a mutation in the circadian gene, CLOCK (Clock-Δ19 mice) perform an elevated zero maze task. In WT mice, basal limbic gamma oscillatory synchrony observed before task performance predicted future anxiety-related behaviors. Additionally, dynamic changes in limbic gamma oscillatory synchrony were observed based on the position of WT mice in the zero maze. Clock-Δ19 mice, which displayed an increased propensity to enter the open section of the elevated maze, showed profound deficits in these anxiety-related circuit processes. Thus, our findings link the anxiety-related behavioral deficits observed in Clock-Δ19 mice with dysfunctional gamma oscillatory tuning across limbic circuits and suggest that alterations in limbic oscillatory circuit function induced by circadian gene polymorphisms may contribute to the behavioral manifestations seen in bipolar mania.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA. kafui.dzirasa@duke.edu
authors.forename: Kafui
authors.initials: K
authors.lastname: Dzirasa
authors.forename: DeAnna L
authors.initials: DL
authors.lastname: McGarity
authors.forename: Anirban
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.forename: David
authors.initials: D
authors.lastname: Dunson
authors.forename: Colleen A
authors.initials: CA
authors.lastname: McClung
authors.forename: Miguel A L
authors.initials: MA
authors.lastname: Nicolelis
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000235:genetics / Q000473:pathology; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology*; D001714:Bipolar Disorder / Q000150:complications* / Q000235:genetics; D056926:CLOCK Proteins / Q000235:genetics; D004195:Disease Models, Animal; D058407:Electroencephalography Phase Synchronization / Q000502:physiology*; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D013057:Spectrum Analysis
chemical_list: D056926:CLOCK Proteins