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Biology (Basel). 2019 Mar 11;8(1). pii: E13. doi: 10.3390/biology8010013.

The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker.

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MRC Laboratory of Molecular Biology, Division of Neurobiology, CB2 0QH Cambridge, UK.
MRC Laboratory of Molecular Biology, Division of Neurobiology, CB2 0QH Cambridge, UK.
UK Dementia Research Institute at Imperial College London, Division of Brain Sciences, Department of Medicine, W12 0NN London, UK.


The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (Synechococcus), fungi (Neurospora), higher plants (Arabidopsis), insects (Drosophila) and mammals (mouse and humans), a common mechanistic motif of delayed negative feedback has emerged as the Deus ex machina for the cellular definition of ca. 24 h cycles. This review will consider, briefly, comparative circadian clock biology and will then focus on the mammalian circadian system, considering its molecular genetic basis, the properties of the suprachiasmatic nucleus (SCN) as the principal circadian clock in mammals and its role in synchronising a distributed peripheral circadian clock network. Finally, it will consider new directions in analysing the cell-autonomous and circuit-level SCN clockwork and will highlight the surprising discovery of a central role for SCN astrocytes as well as SCN neurons in controlling circadian behaviour.


Bmal1; astrocytes; clock; cryptochrome; entrainment; period; photoperiod; sleep; suprachiasmatic

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