Department of Psychiatry, McGill University, Montreal, Canada; Douglas Mental Health University Institute, Montreal, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Canada
Lei Zhu
Department of Psychiatry, McGill University, Montreal, Canada; Douglas Mental Health University Institute, Montreal, Canada
Luc Moquin
Douglas Mental Health University Institute, Montreal, Canada
Maia V Kokoeva
Department of Medicine, McGill University, Montreal, Canada
Alain Gratton
Department of Psychiatry, McGill University, Montreal, Canada; Douglas Mental Health University Institute, Montreal, Canada
Bruno Giros
Department of Psychiatry, McGill University, Montreal, Canada; Douglas Mental Health University Institute, Montreal, Canada; INSERM UMR S1130 CNRS, UMR8246, Sorbonne University, Paris, France
Kai-Florian Storch
Department of Psychiatry, McGill University, Montreal, Canada; Douglas Mental Health University Institute, Montreal, Canada
Ultradian (∼4 hr) rhythms in locomotor activity that do not depend on the master circadian pacemaker in the suprachiasmatic nucleus have been observed across mammalian species, however, the underlying mechanisms driving these rhythms are unknown. We show that disruption of the dopamine transporter gene lengthens the period of ultradian locomotor rhythms in mice. Period lengthening also results from chemogenetic activation of midbrain dopamine neurons and psychostimulant treatment, while the antipsychotic haloperidol has the opposite effect. We further reveal that striatal dopamine levels fluctuate in synchrony with ultradian activity cycles and that dopaminergic tone strongly predicts ultradian period. Our data indicate that an arousal regulating, dopaminergic ultradian oscillator (DUO) operates in the mammalian brain, which normally cycles in harmony with the circadian clock, but can desynchronize when dopamine tone is elevated, thereby producing aberrant patterns of arousal which are strikingly similar to perturbed sleep-wake cycles comorbid with psychopathology.
