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

Hideo Hagihara, Tomoyasu Horikawa, Hironori K. Nakamura, Juzoh Umemori, Hirotaka Shoji, Yukiyasu Kamitani, Tsuyoshi Miyakawa

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Bipolar 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.

Original languageEnglish
Pages (from-to)2784-2796
Number of pages13
JournalCell Reports
Issue number12
Publication statusPublished - 29-03-2016

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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