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Regulation of Daily Locomotor Activity and Sleep by Hypothalamic EGF Receptor Signalling†

  1. Derek J. Chadwick Organizer,
  2. Jamie A. Goode
  1. Achim Kramer1,
  2. Fu-Chia Yang1,‡,
  3. Pamela Snodgrass2,‡,
  4. Xiaodong Li2,‡,
  5. Thomas E. Scammell3,
  6. Fred C. Davis2,
  7. Charles J. Weitz Associate Professor1,*

Published Online: 7 OCT 2008

DOI: 10.1002/0470090839.ch18

Book Title

Molecular Clocks and Light Signalling: Novartis Foundation Symposium 253

Molecular Clocks and Light Signalling: Novartis Foundation Symposium 253

Additional Information

How to Cite

Kramer, A., Yang, F.-C., Snodgrass, P., Li, X., Scammell, T. E., Davis, F. C. and Weitz, C. J. (2008) Regulation of Daily Locomotor Activity and Sleep by Hypothalamic EGF Receptor Signalling, in Molecular Clocks and Light Signalling: Novartis Foundation Symposium 253 (eds D. J. Chadwick and J. A. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470090839.ch18

Author Information

  1. 1

    Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA

  2. 2

    Department of Biology, Northeastern University, Boston, MA 02115, USA

  3. 3

    Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA

  1. ‡

    These authors contributed equally.

*Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA

  1. †

    Abstracted from Kramer et al 2001 with permission from the American Association for the Advancement of Science.

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 28 OCT 2003

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470852835

Online ISBN: 9780470090831

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Summary

The circadian clock in the suprachiasmatic nucleus (SCN) is thought to drive daily rhythms of behaviour by secreting factors that act locally within the hypothalamus. In a systematic screen, we identified transforming growth factor (TGF)α as a likely SCN inhibitor of locomotion. TGFα is expressed rhythmically in the SCN, and when infused into the 3rd ventricle it reversibly inhibits locomotor activity and disrupts circadian sleep–wake cycles. These actions are mediated by epidermal growth factor (EGF) receptors, which we identified on neurons in the hypothalamic subparaventricular zone. Mice with a hypomorphic EGF receptor mutation exhibit excessive daytime locomotor activity and fail to suppress activity when exposed to light. These results implicate EGF receptor signalling in the daily control of locomotor activity, and they identify a neural circuit in the hypothalamus that likely mediates the regulation of behaviour both by the SCN and the retina.

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