6875 Boulevard Lasalle
Biological rhythms and psychopathology.
Linking ultradian and circadian rhythms with psychopathology.
Our lab is interested in the mechanistic basis of sleep-wake cycle aberration that are associated with psychopathology and the role of rhythm generators in this context. To this end, we recently discovered a second brain clock in mice, the dopaminergic ultradian oscillator (DUO), which drives ~4 hour rhythms of motivated arousal. The DUO normally cycles in harmony with the circadian clock, but can desynchronize under high dopamine tone producing much longer rhythms reaching periods of 48hrs and beyond. Intriguingly, the rest-arousal patterns we observe under high-dopamine tone in mice appear particularly reminiscent of certain sleep-wake cycle perturbations associated with schizophrenia and bipolar disease.
We now aim to
• Corroborate the link between psychopathology and DUO dysregulation by studying the effect of psychotropic medication on the daily arousal patterns in psychiatric subjects using actigraphy.
• Delineate the mechanistic principle and locate the site of DUO rhythm generation in mice by employing a variety of molecular genetic, electrophysiological and pharmacological approaches.
• Assess the role of other components of the arousal regulating circuitry in ultradian rhythm generation, such as serotonin and norepinephrine.
Lin, X.W., Blum, I.D., and Storch, K.F. (2015). Clocks within the Master Gland: Hypophyseal Rhythms and Their Physiological Significance. Journal of biological rhythms.
Blum, I.D., Zhu, L., Moquin, L., Kokoeva, M.V., Gratton, A., Giros, B., and Storch, K.F. (2014). A highly tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal. eLife 3.
Chu, A., Zhu, L., Blum, I.D., Mai, O., Leliavski, A., Fahrenkrug, J., Oster, H., Boehm, U., and Storch, K.F. (2013). Global but not gonadotrope-specific disruption of Bmal1 abolishes the luteinizing hormone surge without affecting ovulation. Endocrinology 154, 2924-2935.
Lamia, K.A., Storch, K.F., and Weitz, C.J. (2008). Physiological significance of a peripheral tissue circadian clock. Proceedings of the National Academy of Sciences of the United States of America 105, 15172-15177.
Storch, K.F., and Weitz, C.J. (2009). Daily rhythms of food-anticipatory behavioral activity do not require the known circadian clock. Proceedings of the National Academy of Sciences of the United States of America 106, 6808-6813.
Storch, K.F., Paz, C., Signorovitch, J., Raviola, E., Pawlyk, B., Li, T., and Weitz, C.J. (2007). Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information. Cell 130, 730-741.
Dr. Storch received a Ph.D. from the University of Munich in 1999 for work on the chemotaxis of Archaea conducted at the Max-Planck Institute for Biochemistry in the lab of Dr. Dieter Oesterhelt. He then moved on to receive postdoctoral training at the Neurobiology Department at Harvard Medical School on circadian rhythms in mice in the lab of Dr. Chuck Weitz. In 2008 Dr. Storch joined the faculty of the McGill Dept. of Psychiatry/Douglas Hospital Research Center.
New Investigator Award (CIHR, 2010-2015)
Ian D. Blum
Enhancing circadian clock function in cancer cells inhibits tumor growth. BMC Biol. 2017;15(1):13.
DCC Confers Susceptibility to Depression-like Behaviors in Humans and Mice and Is Regulated by miR-218. Biol Psychiatry. 2017;81(4):306-315.
Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control. Cell Metab. 2016;23(5):797-810.
Clocks within the Master Gland: Hypophyseal Rhythms and Their Physiological Significance. J Biol Rhythms. 2015;30(4):263-76.
Light-regulated translational control of circadian behavior by eIF4E phosphorylation. Nat Neurosci. 2015;18(6):855-62.
Circadian mechanisms of food anticipatory rhythms in rats fed once or twice daily: clock gene and endocrine correlates. PLoS ONE. 2014;9(12):e112451.