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Circadian pacemaking beyond clock genes: Neural network-based coherent oscillation and adaptive phasing by the suprachiamatic nucleus

開催日 2014/9/11
時間 9:00 - 11:00
会場 Room F(302)
Chairperson(s) 本間 さと / Sato Honma (北海道大学大学院医学系研究科 時間医学講座 / Department of Physiol Chronomedicine, Hokkaido University Graduate School of Medicine, Japan)
土居 雅夫 / Masao Doi (京都大学大学院薬学研究科医薬創成情報科学専攻システムバイオロジー分野 / Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan)

Roles of AVP-producing neurons in the central circadian pacemaker of the suprachiasmatic nucleus

  • S1-F-1-4
  • 三枝 理博 / Michihiro Mieda:1 
  • 1:金沢大学大学院 / Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Science, Kanazawa University, Japan 

The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals and entrains to the environmental light/dark cycle. It is composed of multiple types of neurons, and neuronal network properties are integral to normal function of the SCN. However, mechanisms underlying the SCN neuronal network have remained elusive.
As a first step to understand the principle of the SCN network, we generated mice in which Bmal1, an essential clock component, is deleted specifically in the neurons producing arginine vasopressin (AVP), one of the primary neuronal types in the SCN (Avp-Bmal1-/- mice). Avp-Bmal1-/- mice showed lengthening of circadian period (by approximately 1 hour) and activity time (alpha) (by approximately 5 hours, splitting-like phenotype) in constant darkness. When exposed to abrupt 8-h advance of an LD cycle, control mice reentrained progressively to a new LD cycle. In contrast, Avp-Bmal1-/- mice reentrained faster than control mice did with a short transient period of arrhythmic behavior. In Avp-Bmal1-/- mice, expression of Avp, Prokineticin 2, and Rgs16 was drastically reduced in the dorsomedial region of the SCN, where AVP neurons are located. Thus, circadian oscillators of SCN AVP neurons may modulate coupling of cellular oscillators within the SCN for coherent behavior output and determine circadian period by regulating transcription of multiple factors important for the function of these neurons in a coordinated manner.

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