Format

Send to

Choose Destination
Elife. 2014 Dec 29;3. doi: 10.7554/eLife.05105.

A highly tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal.

Author information

1
Department of Psychiatry, McGill University, Montreal, Canada.
2
Douglas Mental Health University Institute, Montreal, Canada.
3
Department of Medicine, McGill University, Montreal, Canada.

Abstract

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.

KEYWORDS:

arousal; chronobiology; dopamine; dopamine transporter; mouse; neuroscience; oscillator; ultradian

Comment in

PMID:
25546305
PMCID:
PMC4337656
DOI:
10.7554/eLife.05105
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center