Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ARNTL Transcription Factors
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Action Potentials / drug effects
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Biological Clocks / physiology*
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CLOCK Proteins
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Cell Cycle Proteins
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Circadian Rhythm / physiology*
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Cycloheximide / pharmacology
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Gene Expression
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Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
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Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
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Luminescence
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Mice
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Mice, Knockout
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Mice, Transgenic
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Neurons / physiology*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Organ Culture Techniques
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Period Circadian Proteins
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Promoter Regions, Genetic
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Protein Synthesis Inhibitors / pharmacology
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Signal Transduction
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Sodium / metabolism
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Suppression, Genetic
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Suprachiasmatic Nucleus / cytology
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Suprachiasmatic Nucleus / physiology*
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Tetrodotoxin / pharmacology
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Transcription, Genetic
Substances
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ARNTL Transcription Factors
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Bmal1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle Proteins
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Nuclear Proteins
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Per1 protein, mouse
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Per2 protein, mouse
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Period Circadian Proteins
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Protein Synthesis Inhibitors
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Trans-Activators
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Transcription Factors
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Tetrodotoxin
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Cycloheximide
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Sodium
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Glyceraldehyde-3-Phosphate Dehydrogenases
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CLOCK Proteins
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Clock protein, mouse