RT Journal Article
SR Electronic
T1 Impaired Limbic Gamma Oscillatory Synchrony during Anxiety-Related Behavior in a Genetic Mouse Model of Bipolar Mania
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6449
OP 6456
DO 10.1523/JNEUROSCI.6144-10.2011
VO 31
IS 17
A1 Kafui Dzirasa
A1 DeAnna L. McGarity
A1 Anirban Bhattacharya
A1 Sunil Kumar
A1 Joseph S. Takahashi
A1 David Dunson
A1 Colleen A. McClung
A1 Miguel A. L. Nicolelis
YR 2011
UL http://www.jneurosci.org/content/31/17/6449.abstract
AB 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.