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Brain Structure and Function

, Volume 224, Issue 1, pp 19–31 | Cite as

A suprachiasmatic-independent circadian clock(s) in the habenula is affected by Per gene mutations and housing light conditions in mice

  • Nora L. Salaberry
  • Hélène Hamm
  • Marie-Paule Felder-Schmittbuhl
  • Jorge MendozaEmail author
Original Article

Abstract

For many years, the suprachiasmatic nucleus (SCN) was considered as the unique circadian pacemaker in the mammalian brain. Currently, it is known that other brain areas are able to oscillate in a circadian manner. However, many of them are dependent on, or synchronized by, the SCN. The Habenula (Hb), localized in the epithalamus, is a key nucleus for the regulation of monoamine activity (dopamine, serotonin) and presents circadian features; nonetheless, the clock properties of the Hb are not fully described. Here, we report, first, circadian expression of clock genes in the lateral habenula (LHb) under constant darkness (DD) condition in wild-type mice which is disturbed in double Per1−/−-Per2Brdm1 clock-mutant mice. Second, using Per2::luciferase transgenic mice, we observed a self-sustained oscillatory ability (PER2::LUCIFERASE bioluminescence rhythmicity) in the rostral and caudal part of the Hb of arrhythmic SCN-ablated animals. Finally, in Per2::luciferase mice exposed to different lighting conditions (light-dark, constant darkness or constant light), the period or amplitude of PER2 oscillations, in both the rostral and caudal Hb, were similar. However, under DD condition or from SCN-lesioned mice, these two Hb regions were out of phase, suggesting an uncoupling of two putative Hb oscillators. Altogether, these results suggest that an autonomous clock in the rostral and caudal part of the Hb requires integrity of circadian genes to tick, and light information or SCN innervation to keep synchrony. The relevance of the Hb timing might reside in the regulation of circadian functions linked to motivational (reward) and emotional (mood) processes.

Keywords

Circadian Habenula Per2 luciferase Suprachiasmatic Clock genes 

Notes

Acknowledgements

We thank deeply Prof. Urs Albrecht (University of Fribourg) for providing the Per1−/−Per2Brdm1 mutant mice. Per1 and Cry2 plasmids were kindly donated by Prof. H. Okamura (Kyoto University, Japan). mClock and rRevErbα plasmids were generously provided by Prof. J. Takahashi (Northwestern University) and Dr. Hugues Dardente (University of Tours), respectively. We thank the personal of the Chronobiotron Platform (UMS 3414, Strasbourg) for animal care. Funding sources of the present study were provided by the Agence National de la Recherche (ANR-14-CE13-0002-01 ADDiCLOCK JCJC to JM and NLS PhD fellow) and the Centre National de la Recherche Scientifique (JM and MPFS).

Compliance with ethical standards

Conflict of interest

Authors declare no potential conflicts of interest.

Human or animal rights

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Supplementary material

429_2018_1756_MOESM1_ESM.doc (4 mb)
Supplementary material 1 (DOC 4057 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Cellular and Integrative Neurosciences, CNRS UPR-3212StrasbourgFrance

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