Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model

•Gene expressions of αCaMKII (Camk2a) mutant mice, a bipolar disorder model, are analyzed•Gene expression patterns in the mouse brain retrospectively predict behavioral state•Expression of many circadian genes correlates with infradian rhythm behavior•Expression of molecules in the cAMP/CREB pathway also correlates with the behavior

SummaryBipolar disorder, also known as manic-depressive illness, causes swings in mood and activity levels at irregular intervals. Such changes are difficult to predict, and their molecular basis remains unknown. Here, we use infradian (longer than a day) cyclic activity levels in αCaMKII (Camk2a) mutant mice as a proxy for such mood-associated changes. We report that gene-expression patterns in the hippocampal dentate gyrus could retrospectively predict whether the mice were in a state of high or low locomotor activity (LA). Expression of a subset of circadian genes, as well as levels of cAMP and pCREB, possible upstream regulators of circadian genes, were correlated with LA states, suggesting that the intrinsic molecular circuitry changes concomitant with infradian oscillatory LA. Taken together, these findings shed light onto the molecular basis of how irregular biological rhythms and behavior are controlled by the brain.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide