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Neuron. 2015 Apr 8;86(1):264-75. doi: 10.1016/j.neuron.2015.02.036. Epub 2015 Mar 19.

Clock genes control cortical critical period timing.

Author information

1
Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA; F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2
Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
3
Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA; F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: hensch@mcb.harvard.edu.

Abstract

Circadian rhythms control a variety of physiological processes, but whether they may also time brain development remains largely unknown. Here, we show that circadian clock genes control the onset of critical period plasticity in the neocortex. Within visual cortex of Clock-deficient mice, the emergence of circadian gene expression was dampened, and the maturation of inhibitory parvalbumin (PV) cell networks slowed. Loss of visual acuity in response to brief monocular deprivation was concomitantly delayed and rescued by direct enhancement of GABAergic transmission. Conditional deletion of Clock or Bmal1 only within PV cells recapitulated the results of total Clock-deficient mice. Unique downstream gene sets controlling synaptic events and cellular homeostasis for proper maturation and maintenance were found to be mis-regulated by Clock deletion specifically within PV cells. These data demonstrate a developmental role for circadian clock genes outside the suprachiasmatic nucleus, which may contribute mis-timed brain plasticity in associated mental disorders.

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PMID:
25801703
PMCID:
PMC4392344
DOI:
10.1016/j.neuron.2015.02.036
[Indexed for MEDLINE]
Free PMC Article

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