Role of GABA in the regulation of the central circadian clock of the suprachiasmatic nucleus

  • Daisuke Ono
  • Ken-ichi Honma
  • Yuchio Yanagawa
  • Akihiro Yamanaka
  • Sato Honma
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Abstract

In mammals, circadian rhythms, such as sleep/wake cycles, are regulated by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of thousands of individual neurons, which exhibit circadian rhythms. They synchronize with each other and produce robust and stable oscillations. Although several neurotransmitters are expressed in the SCN, almost all SCN neurons are γ-amino butyric acid (GABA)-ergic. Several studies have attempted to understand the roles of GABA in the SCN; however, precise mechanisms of the action of GABA in the SCN are still unclear. GABA exhibits excitatory and/or inhibitory characteristics depending on the circadian phase or region in the SCN. It can both synchronize and destabilize cellular circadian rhythms in individual SCN cells. Differing environmental light conditions, such as a long photoperiod, result in the decoupling of circadian oscillators of the dorsal and ventral SCN. This is due to high intracellular chloride concentrations in the dorsal SCN. Because mice with functional GABA deficiency, such as vesicular GABA transporter- and glutamate decarboxylase-deficient mice, are neonatal lethal, research has been limited to pharmacological approaches. Furthermore, different recording methods have been used to understand the roles of GABA in the SCN. The excitability of GABAergic neurons also changes during the postnatal period. Although there are technical difficulties in understanding the functions of GABA in the SCN, technical developments may help uncover new roles of GABA in circadian physiology and behavior.

Keywords

Circadian rhythm Suprachiasmatic nucleus Clock gene Cellular networks GABA Photoperiod 
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Notes

Acknowledgements

This work was supported in part by the Uehara Memorial Foundation, the Nakajima Foundation, GSK Japan Research Grant 2015, the Project for Developing Innovation Systems of the MEXT, and Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program, Ministry of Education, Culture, Sports, Science and Technology, Japan, and JSPS KAKENHI (Nos. 15H04679, 26860156, 15K12763).

Compliance with ethical standards

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Daisuke Ono
    • 1
  • Ken-ichi Honma
    • 2
  • Yuchio Yanagawa
    • 3
  • Akihiro Yamanaka
    • 1
  • Sato Honma
    • 2
  1. 1.Department of Neuroscience II, Research Institute of Environmental MedicineNagoya UniversityNagoyaJapan
  2. 2.Research and Education Center for Brain ScienceHokkaido University Graduate School of MedicineSapporoJapan
  3. 3.Department of Genetic and Behavioral NeuroscienceGunma University Graduate School of MedicineMaebashiJapan

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