The Douglas Hospital Research Centre

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.