Synchronization of cellular clocks in the suprachiasmatic nucleus.
Individual cellular clocks in the suprachiasmatic nucleus (SCN), the circadian center, are integrated into a stable and robust pacemaker with a period length of about 24 hours. We used real-time analysis of gene expression to show synchronized rhythms of clock gene transcription across hundreds of neurons within the mammalian SCN in organotypic slice culture. Differentially phased neuronal clocks are topographically arranged across the SCN. A protein synthesis inhibitor set all cell clocks to the same initial phase and, after withdrawal, intrinsic interactions among cell clocks reestablished the stable program of gene expression across the assemblage. Na+-dependent action potentials contributed to establishing cellular synchrony and maintaining spontaneous oscillation across the SCN.
Yamaguchi
Shun
S
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Isejima
Hiromi
H
Matsuo
Takuya
T
Okura
Ryusuke
R
Yagita
Kazuhiro
K
Kobayashi
Masaki
M
Okamura
Hitoshi
H
D056930:ARNTL Transcription Factors; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000502:physiology*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D013489:Suppression, Genetic; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D003513:Cycloheximide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D011500:Protein Synthesis Inhibitors; D012964:Sodium; D013779:Tetrodotoxin; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C538944:Clock protein, mouse