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Cell-autonomous clock of astrocytes drives circadian behavior in mammals

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Science  11 Jan 2019:
Vol. 363, Issue 6423, pp. 187-192
DOI: 10.1126/science.aat4104

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Astrocytes can drive the master clock in the brain

The neurons of the suprachiasmatic nucleus (SCN) of the hypothalamus function as a central circadian clock, coordinating mammalian physiology with the 24-hour light-dark cycle. Brancaccio et al. found that these neurons have help from neighboring astrocytes (see the Perspective by Green). In mice lacking the Cry gene, which encodes a critical clock component, restoration of Cry expression and molecular clock function in the astrocytes, but not the neighboring neurons, restored rhythmic transcriptional oscillations in the SCN and reestablished circadian behaviors in the mice.

Science, this issue p. 187; see also p. 124

Abstract

Circadian (~24-hour) rhythms depend on intracellular transcription-translation negative feedback loops (TTFLs). How these self-sustained cellular clocks achieve multicellular integration and thereby direct daily rhythms of behavior in animals is largely obscure. The suprachiasmatic nucleus (SCN) is the fulcrum of this pathway from gene to cell to circuit to behavior in mammals. We describe cell type–specific, functionally distinct TTFLs in neurons and astrocytes of the SCN and show that, in the absence of other cellular clocks, the cell-autonomous astrocytic TTFL alone can drive molecular oscillations in the SCN and circadian behavior in mice. Astrocytic clocks achieve this by reinstating clock gene expression and circadian function of SCN neurons via glutamatergic signals. Our results demonstrate that astrocytes can autonomously initiate and sustain complex mammalian behavior.

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