Cellular clocks in AVP neurons of the SCN are critical for interneuronal coupling regulating circadian behavior rhythm.
The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of behavior rhythms. When exposed to an abrupt 8-hr advance of the light/dark cycle, these mice reentrained faster than control mice did. In these mice, the circadian expression of genes involved in intercellular communications, including Avp, Prokineticin 2, and Rgs16, was drastically reduced in the dorsal SCN, where AVP neurons predominate. In slices, dorsal SCN cells showed attenuated PER2::LUC oscillation with highly variable and lengthened periods. Thus, Bmal1-dependent oscillators of AVP neurons may modulate the coupling of the SCN network, eventually coupling morning and evening behavioral rhythms, by regulating expression of multiple factors important for the network property of these neurons.
Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. Electronic address: mieda@med.kanazawa-u.ac.jp.
Michihiro
M
Mieda
Photonic Bioimaging Section, Research Center for Cooperative Projects, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Daisuke
D
Ono
Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan.
Emi
E
Hasegawa
Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Hitoshi
H
Okamoto
Department of Chronomedicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Ken-Ichi
K
Honma
Department of Chronomedicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Sato
S
Honma
Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan.
Takeshi
T
Sakurai
D056930:ARNTL Transcription Factors / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D001127:Arginine Vasopressin