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Updated: Apr 15, 2026
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
Clock genes control cortical critical period timing
Yohei Kobayashi1, Zhanlei Ye2, Takao K Hensch1
1Center 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.
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.
Insights
Circadian clock genes regulate critical period plasticity in the neocortex. Disruptions in these genes, particularly in parvalbumin (PV) cells, delay visual development and maturation.
Area of Science:
- Neuroscience
- Developmental Biology
- Chronobiology
Background:
- Circadian rhythms influence physiological processes but their role in brain development is unclear.
- Critical period plasticity in the neocortex is essential for sensory system maturation.
Purpose of the Study:
- To investigate the role of circadian clock genes in timing neocortical development and plasticity.
- To determine if circadian clock genes influence the maturation of inhibitory networks and visual acuity.
Main Methods:
- Utilized Clock-deficient mice to examine the impact on circadian gene expression and parvalbumin (PV) cell network maturation.
- Assessed visual acuity changes following monocular deprivation and manipulated GABAergic transmission.
- Employed conditional gene deletion of Clock or Bmal1 specifically in PV cells.
Main Results:
- Clock deficiency dampened circadian gene expression and slowed PV cell network maturation in the visual cortex.
- Monocular deprivation-induced loss of visual acuity was delayed and could be rescued by enhancing GABAergic transmission.
- Conditional deletion of Clock or Bmal1 in PV cells mimicked the effects of total Clock deficiency, affecting synaptic and homeostatic gene sets.
Conclusions:
- Circadian clock genes play a crucial role in timing neocortical development and critical period plasticity.
- Disruptions in these genes within PV cells impact synaptic function and cellular homeostasis, leading to mis-timed brain development.
- This highlights a potential link between circadian dysfunction and mental disorders associated with mis-timed brain plasticity.
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