Ultradian clocks and the striatal dopaminergic system.

Human and other animal behavior and physiology commonly show a circadian rhythm, a change in behavior that follows an approximate 24 hour cycle. Animals and humans also show patterns in their behavior, such as mealtime intervals, that are not fixed to the approximately 24-hour circadian cycle, but instead have periods that are substantially less than (i.e., ‘ultradian’) or greater than (i.e., ‘infradian’) 24 hours (see also this review).

The article below suggests that both ultradian and infradian rhythms may be set by the dopaminergic system. Deliberately altering such settings might some day help the insomnia disorders so common in those with mental illnesses as well as sleep disorders in conditions such as Parkinson disease.

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ABSTRACT

A highly tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal

Ian D Blum, Lei Zhu, Luc Moquin, Maia V Kokoeva, Alain Gratton, Bruno Giros, Kai-Florian Storch

DOI: http://dx.doi.org/10.7554/eLife.05105

Published December 29, 2014

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.

DOI: http://dx.doi.org/10.7554/eLife.05105.001