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Clock controls circadian period in isolated suprachiasmatic nucleus neurons

Nature Neuroscience volume 1, pages 708–713 (1998)Cite this article

Abstract

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals, and one molecular regulator of circadian rhythms is the Clock gene. Here we studied the discharge patterns of SCN neurons isolated from Clock mutant mice. Long-term, multielectrode recordings showed that heterozygous Clock mutant neurons have lengthened periods and that homozygous Clock neurons are arrhythmic, paralleling the effects on locomotor activity in the animal. In addition, cells in dispersals expressed a wider range of periods and phase relationships than cells in explants. These results suggest that the Clock gene is required for circadian rhythmicity in individual SCN cells and that a mechanism within the SCN synchronizes neurons and restricts the range of expressed circadian periods.

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Figure 1: Circadian rhythms in wheel-running activity for representative wild-type and Clock mutant mice.
Figure 2: Dispersed SCN cells express a range of circadian periods and phase relationships within the same culture on multielectrode plates.
Figure 3: Firing-rate patterns of dispersed SCN cells from wild-type and Clock mutant mice show that the Clock mutation affects period length in heterozygous SCN cells and period stability in homozygotes.
Figure 4: The Clock mutation lengthened the mean free-running period of SCN cells.
Figure 5: The range of circadian periods in wild-type SCN cells increases only after the normal tissue organization has been disrupted.

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Acknowledgements

We wish to thank David King for guidance in allele-specific genotyping, Martha Vitaterna and Sharon Low-Zeddies for providing mice, Naomi Ihara, Michael Menaker and Shin Yamazaki for assistance with behavioral assays, and Christine Harrer, Li Miao and John Williamson for technical assistance. We are also grateful to Martin Straume for statistical advice and to Tom Breeden for programming the data acquisition system. This work was supported by the NSF Center for Biological Timing and a NIH Endocrine Training grant to E.D.H. J.S.T. is an Investigator in the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. NSF Center for Biological Timing,

    Erik D. Herzog, Joseph S. Takahashi & Gene D. Block

  2. Dept. of Biology, Gilmer Hall, University of Virginia, Charlottesville, 22903, Virginia, USA

    Erik D. Herzog & Gene D. Block

  3. Howard Hughes Medical Institute, Dept. of Neurobiology and Physiology, Northwestern University, 2153 N. Campus Road, Evanston, 60208, Illinois, USA

    Joseph S. Takahashi

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  1. Erik D. Herzog
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Correspondence to Erik D. Herzog.

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Herzog, E., Takahashi, J. & Block, G. Clock controls circadian period in isolated suprachiasmatic nucleus neurons. Nat Neurosci 1, 708–713 (1998). https://doi.org/10.1038/3708

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