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

  1. Ian D Blum
  2. Lei Zhu
  3. Luc Moquin
  4. Maia V Kokoeva
  5. Alain Gratton
  6. Bruno Giros
  7. Kai-Florian Storch  Is a corresponding author
  1. McGill University, Canada
  2. Douglas Mental Health University Institute, Canada
Research Article
  • Cited 65
  • Views 8,986
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Cite this article as: eLife 2014;3:e05105 doi: 10.7554/eLife.05105

Abstract

Ultradian (~4 h) 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.

Article and author information

Author details

  1. Ian D Blum

    Department of Psychiatry, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Lei Zhu

    Department of Psychiatry, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Luc Moquin

    Douglas Mental Health University Institute, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Maia V Kokoeva

    Department of Medicine, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Alain Gratton

    Department of Psychiatry, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Bruno Giros

    Department of Psychiatry, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Kai-Florian Storch

    Department of Psychiatry, McGill University, Montreal, Canada
    For correspondence
    florian.storch@mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experimental procedures were performed in accordance with the Canadian Council on Animal Care guidelines and approved by the McGill University Animal Care Committee (animal use protocol #2010-5945).

Reviewing Editor

  1. Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States

Publication history

  1. Received: October 10, 2014
  2. Accepted: December 28, 2014
  3. Accepted Manuscript published: December 29, 2014 (version 1)
  4. Version of Record published: February 12, 2015 (version 2)

Copyright

© 2014, Blum et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Further reading

Further reading

  1. Dopamine drives an "ultradian" clock with a period of around four hours in mice.

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